How old are you, really?

It seems like a simple question. Its based on when youre born. Yet we all know people who seem much younger than their chronological age. They have radiant skin and hair. They seem sharper than their age would suggest. Theyre highly active with astonishing energy.

Why? Studies have repeatedly shown that cells, tissues, and people have a biological age that may or may not correspond to how old they are in terms of birthdays. Longevity scientists have taken note. As they look into what makes us age, one main metric pops up: a biological aging clocka measure that reflects your bodys age irrespective of your years on Earth.

One of the most popular aging clocks dives deep into our cells. As we age, our genomes add on chunks of chemicals that alter their gene expression. These markers, dubbed epigenetic modifications, normally just tack on and off like Velcro. But with age, certain bits of the genome add far more chunks, which essentially work to shut the genes off.

In other words, our cells have an epigenetic age (EpiAge). But what, if anything, does the clock mean for longevity?

Dr. Steve Horvath had his eye on extending lifespan ever since he was a teenager. A biomathematician, he set his eyes on using computation modeling and AI to understand how to extend life.

But to find the key, he needed a focus. Horvaths idea stemmed from epigeneticsa powerful way our bodies control DNA expression without altering the DNA strands themselves. Epigenetics is an extremely fluid dance, with multiple chemical components latching onto or falling off of DNA strands. The epigenetic dance changes with age, though some changes seem consistent across time. This led Horvath to ask: can we use these epigenetic markers to gauge a cells age?

Apparently, the answer is yes. After gathering and analyzing over 13,000 human samples, Horvath found an impressive measuring tape for aging. The key was a type of epigenetic modification called methylation, which tends to rest on DNA spots dubbed CpG islands. (We all need a summer break!)

His team developed an algorithm for biological agea cellular biological clockthat impressed longevity researchers with its accuracy throughout the body. Rather than a one-off, EpiAge seems to work for multiple organs and tissues, potentially shining light on how aging happens.

I wanted to develop a method that would work in many or most tissues. It was a very risky project, Horvath said at the time.

The clocks median error was a measly 3.6 years, meaning that it could gauge a persons age within 43 months. Even more impressive, the clock used a simple statistical model, which looked at a certain type of epigenetic modificationDNA methylationat just two target sites on DNA. All it took was a saliva sample. With more work, Horvath found even more patterns that reflected the age of certain types of cells, such as neurons and blood cells. The test was amazingly good, said Kevin Bryant at Zymo Research, a biotechnology company in Irvine, California at the time.

EpiAge also began looking under the veil. The discrepancy between epigenetic age as estimated by these clocks, and chronological age is referred to as EpiAge acceleration, the authors said. Epidemiological studies have linked EpiAge acceleration to a wide variety of pathologies, health states, lifestyle, mental state, and environmental factors, indicating that epigenetic clocks tap into critical biological processes that are involved in aging.

Yet one glaring question remained: what exactly is the EpiAge clock measuring?

If youre having trouble linking epigenetic modifications to aging, I feel ya. How and why do what are essentially fridge magnets for the genome change anything?

Let me introduce you to the wheel of aging.

Zooming in on our genes, the genome becomes more unstablemeaning that theres more chances for mutations. Telomeres, the protective cap on the genes, waste away. Proteins start behaving wonkily, sometimes forming into clumps that clog up the cells waste disposal system, potentially leading to Alzheimers and other neurodegenerative disorders. The cells energy factory, the mitochondria, sputters and malfunctions. Cells can no longer sense nutrients floating around. Even worse, some cells give up completely and turn into senescent zombie cellsthey dont die, but dont perform normal functions, instead spewing out toxic immune chemicals.

The thing is, we dont know why these different types of aging behaviors happen. And when measuring age, we dont know how aging clocks correspond to these hallmarks. Its partly why there are multiple aging clocks. EpiAge is one. Another is (not kidding) Skin & blood, which predicts lifespan and relates to many age-related conditions.

In a new study, published in Nature Aging, Horvath and Dr. Ken Raj at Altos Labs took a first step at linking the epigenetic clock to the hallmarks of aging. Using donated human cells from 14 healthy peoplegrown inside containers in the labthe team split the cells into four groups. One was zapped with radiation, another tweaked to become cancerous, and a third that turned into zombie senescent cells. The fourth group was left alone without any treatment.

These treatments reflect major hallmarks of aging, the authors explained. Radiation in small doses, for example, destabilizes the genome that mimics aging, and the cells became senescent is just two weeks. Cancer-like cells also aged heavily in just a few days. Yet surprisingly, the cells didnt age according to EpiAge, even when tested in other cells. These results, obtained through investigation using different primary human and mouse cells and multiple radiation doses and regimens, demonstrate that epigenetic agingis not affected by genomic instability induced by radiation-induced DNA breaks, the authors said.

In other words, what EpiAge measureschanges to a cells CpG epigenomedoesnt necessarily predict a cells zombie senescence status. Similarly, the clock didnt seem to match up with telomere problems or general genome stability.

What did match up? Energy. Breaking it down, EpiAge is associated with a cells ability to sense nutrientsa key signal that tells it to grow, reproduce, or shrivel. Another associate is mitochondria activity, which generates power for the cell. Finally, EpiAge also seems to reflect the amount of stem cells in the samples, which changes starting early.

The observation that aging begins so early in life is possible because age can now be measured based on the biology of the cell instead of the passing of time, the authors said. For aging clocks, this measurement allows interrogation of the link between age and longevity.

While aging clocks are increasingly becoming mainstream, the question is what exactly each measures. The excitement following the development of epigenetic clocks has been tinged with uncertainty as to the meaning of their measurements.

This study is one of the first to link a powerful aging clock to the hallmarks of aging. The connection of epigenetic aging to four of the hallmarks of aging implies that these hallmarks are also mutually connected at deeper levels, the authors wrote.

In other words, weve started peeking into what unites the multiple veins of aging. The absence of a connection between the other aging hallmarks and epigenetic aging suggests that aging is a consequence of multiparallel mechanisms, the authors said. Some may be because of epigenetic changes; others simply due to wear and tear. Bring on the aging multiverse of madness.

Image Credit:Icons8_team from Pixabay

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According to reports, currently, 64.34 million people suffer from heart failure worldwide[1]. Furthermore, the number of patients with end-organ heart failure is rising, leading to an all-time high in the number of people waiting for an organ transplant[2]. Several strategies have been devised to increase this strained supply of heart for transplantation, including expanding donor criteria[3], use of advanced perfusion machines such as organ care systems (OCS) to improve viability[4], use of normothermic regional perfusion (NRP) in donor from cardiac death (DCD) hearts, and xenotransplantation. Recently, the focus has shifted to new procedures using regenerative cells, angiogenesis factors, biological matrices, biocompatible synthetic polymers, and online registry systems that utilize bioimplants. These advanced technologies are collectively referred to as tissue engineering[5-8]. Ultimately, the goal is to grow a heart de novo. In addition to the unlimited organ supply, the new organ would be antigenically identical to the recipient as the recipients cells would be used, eliminating the need for immunosuppressive agents.

Even though bioengineering a fully functioning heart is in its infancy, huge strides have been made in achieving this goal. Scientists have been able to bioengineer models of the heart, lungs, pancreas, liver, and kidney. An important strategy for supporting the recipients cells and creating an autologous tissue/organ is to create a mechanical, geometrical, and biological environment that closely mimics the native organs properties. The breakthrough in growing an artificial heart was the invention of the decellularization of extracellular matrix (ECM), which maintains the native vascular network[9]. Numerous tissues and organs have been engineered using decellularization, including livers [10], lungs[11], kidneys[12], corneas[13], bladders[14], vasculature[15], articular cartilage[16], intestines[17], and hearts[18]. There has been some success in engineering a heart in the lab. Although technological innovations and biological model systems have resulted in great progress, constructing such complicated tissue structures effortlessly remains a challenge. This review aims to outline the techniques involved in bioengineering a heart in the lab and the challenges involved in developing it into a viable organ for transplantation (Figure 1).

The human heart comprises various cells, each specialized to perform a specific task. A human heart contains roughly 2-3 billion cardiomyocytes, making up only about one-third of its total cells [19]. Additionally, other cells include endothelial cells, fibroblasts, and specialized conducting cells like Purkinje fibers. On top of that, structural scaffolds support the functions of cells arranged into structures, such as vessels, muscles, and nerves. These scaffolds mainly consist of polysaccharides and proteoglycans embedded in complex sugars and chemokines matrix, allowing the heart to coordinate its mechanical and electrical functions [20,21]. Sprawled around this is a collection of protein fibers such as collagen and elastin, which confers mechanical strength to the heart and allow for the constant loading and unloading forces[22,23]. Thus, it is necessary to construct a scaffold around which the specialized cells can grow and maintain vitality through blood perfusion to recreate a functioning heart in a laboratory [24] (Figure 2).

Extracellular matrix (ECM) and cells in an organ display a dynamic reciprocity, whereby the ECM constantly adapts to the demands of the cells[25], and selecting the appropriate scaffold is the key component for growing a viable organ in the lab. Researchers have also studied various synthetic scaffolds as potential surrogates for the ECM, but none can replicate its intricacy or structure compared to native ECM. It is possible to vascularize synthetic materials such as polylactic acid (PLLA) and polylactic glycolic acid (PLGA) and to produce them consistently[26,27]. The significant advantage of synthetic ECM is its production scalability as it does not require to be harvested from living tissue, but these do not match the native myocardiums tensile strength. Hydrogels have also been studied extensively and even accepted by the Food and Drug Administration for drug delivery and adjunct for cell therapy. Hydrogels consist of a cross-linked hydrophilic polymer matrix with over 30% water content [28]. However, they have poor cell retention [29] or poor tensile strength [30]; hence, they are not feasible as a primary scaffold for constructing an organ. Decellularizing the whole heart and leaving the ECM serves as a potential solution to this problem with the particular advantage of having a balanced composition of all the proteins present physiologically [31].

The Badylak laboratory developed the first technique for decellularizing tissue[32]. This process involved the removal of the cell, leaving only the ECM, which retained its composition, architecture, and mechanical properties. There are several methods for removing cells from the ECM. These methods include physical methods (e.g., freeze/thaw cycles), enzymatic degradation (e.g., trypsin), and removal by using chemicals (e.g., sodium dodecyl sulfate)[33]. Ott et al. noted that decellularization could be achieved with different detergent solutions. Comparative studies on decellularization methods have mixed results regarding the superiority of different techniques [34-37]. Based on the results, the sodium dodecyl sulfate (SDS) solution was found to be the best [18]. However, a few studies have suggested that SDS treatment causes degradation of the ECM with a reduction in elastin, collagen, and glycosaminoglycans (GAG) content [34]. The decellularization process utilizes 1% SDS perfused through the coronary circulation, followed by washing it with de-ionized water and subsequently 1% Triton-X-100 (Sigma). Finally, the organ remnant is washed with phosphate-buffered saline (PBS) wash buffer, antibiotic, and protease, leaving a decellularized ECM[38,39]. Using this technique, they decellularized the heart, reseeded it with neonatal cardiac cells, and grew the first beating rodent heart in the lab [18]. Decellularized tissue provides a dynamic environment for the orientation and coupling of cells and facilitates the exchange of nutrients and oxygen throughout the depth of the tissue. Moreover, this process efficiently removes both allogeneic and xenogeneic antigens, possibly preventing the need for immunosuppressants [33], which is especially important as one of the causes of heart failure in transplanted hearts is myocardial fibrosis from chronic rejection [40]. This process can be potentially avoided by using a decellularized heart to generate an ECM scaffold which can then be repopulated using the recipients cells.

Researchers have used animal heart ECM and human heart ECM scaffolds to provide this decellularized ECM scaffold. The porcine heart has often been deemed suitable for its similarity with the human heart [41]. As decellularization removes most of the cells, much of the antigen load is removed. However, the porcine heart ECM contains -1,3-galactose epitope (-gal), which can stimulate an immune response [42,43]. One way to circumvent this is to use pigs lacking -gal epitope, but this technique needs further research. Another possible problem with using a porcine heart is the possible risk of horizontal transmission of porcine viruses like the porcine endogenous retrovirus, cytomegalovirus, HSB, circovirus, etc. [44,45]. Although a few tests can detect the presence of these viruses, they have poor sensitivity, and hence further work has to be done [46].

A cadaveric heart that is unfit for transplant can also be used to harvest an ECM scaffold [47]. The only drawback to this is that it may not always be possible to achieve the desired level of tissue engineering fidelity with these matrices because they may be damaged or diseased. Moreover, there is an assumption that they are superior for the growth and differentiation of human cells, but there is no robust evaluation to support this assumption. The method for decellularization of the cadaveric human heart is similar to that of other animals, utilizing 1% SDS and 1% Triton X-100, with the only difference being a longer perfusion time for these chemicals [48,49].

These cells are highly specialized and terminally differentiated, and hence, they do not proliferate normally. Therefore, to repopulate a human-sized scaffold, autologous human cardioblasts must be isolated or expanded in large quantities. Hence, for the recellularization of ECM, a method of inducing progenitor cells had to be devised. Thus, the discovery of methods to reprogram or induce adult cells into pluripotent stem cells was a significant milestone in stem cell biology and tissue bioengineering[50-52].

Once we have the cells for repopulation of ECM, recellularization is required to achieve a functional organ product for implantation. For recellularization to be achieved, choosing appropriate cell sources, seeding cells optimally, and cultivating them using organ-specific cultures are needed [24]. Cells from fetuses and adults, embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) have all been used[24]. Obtained with ease and ethically, stem cells from bone marrow stroma or adipose tissue (MSC) have shown promise as the ideal cells for recellularization [53]. In addition, human somatic cells can be reprogrammed to produce iPSCs, and they exhibit properties similar to ESCs [54].

A potential solution to the problem of getting a large number of human cells for tissue engineering or other regenerative medicine approaches is the ability to produce iPSCs from readily available autologous cells such as fibroblasts or blood cells[55,56]. The only drawback to using iPSCs is the possibility of teratoma formation due to its pluripotent nature [48,57]. However, the potential solution to this problem is to allow controlled differentiation toward a cardiac lineage before implantation into the ECM [58]. Although previously any attempts to produce iPSCs would result in karyotype instability [59], recent advances have been made with iPSCs maintaining chromosomal integrity [60]. These advances have ushered astep forward in the pursuit of creating viable organs in the lab.

Cell seeding techniques depend on the type of organ being engineered, and, for the heart, it usually involves seeding by perfusion through the vascular tree [24]. This step is called re-endothelization and is usually the first step to recellularization. A dynamic communication between endothelial cells and cardiomyocyte populations occurs via direct cell interactions and the secretion of various factors[61,62]. It is evident from multiple reports that seeding endothelial cell populations and cardiomyocyte populations simultaneously provides functional benefits that aid in maintaining the recellularization process [63]. Interestingly, endothelial cells have also demonstrated the ability to differentiate into cardiomyocytes in other cardiomyocyte cells [64], which may aid in more efficient recellularization. Moreover, besides the advantage, the recellularization of both the vascular tree and the heart parenchyma must be uniform to prevent two key issues in the heart, namely, thrombogenesis[65] and arrhythmogenesis[66].

Improved cell concentration and diffusion over the scaffold can be achieved by optimizing the mechanical environment, scaffold coating, and cell perfusion systems by using multiple perfusion routes simultaneously, which for the heart involves both direct intramyocardial injections and perfusion of the vascular tree [67]. However, the potential problem with intramyocardial injections is that even though the injection site shows dense cellularity, the cells are generally poorly distributed throughout the scaffold [58]. Moreover, sequential injections of cardiac cells will likely be required to rebuild the chamber parenchyma, which may compromise matrix integrity [48]. Nevertheless, given that cardiac cells include fibroblasts, in which ECM is produced and secreted, there is a possibility that endogenous matrix repair may occur after cell seeding to help resolve this issue [62].

While sourcing cells for recellularization using stem cells is a work in progress, multiple studies have explored ways to develop mature cardiomyocytes derived from iPSCs that are more physiologically similar to native cardiomyocytes [68,69]. One of the most recent cardiac constructs was engineered using PSC-derived cardiac cells in a ratio of equal cardiomyocyte and noncardiomyocyte cells, cultured in serum-free media [70]. Cardiomyocytes cultivated in this method were elongated, had organized sarcomeres and distinguished bands, and exhibited increased contractility [70]. It is encouraging to see these results that stem cells can be used to produce cardiomyocytes similar to native mature cells, reinforcing the notion that stem cells can be a cardiac cell source.

After enough cells have been seeded onto an organ scaffold, cell culture is required. A bioreactor is required for perfusion and provides a nutrient-rich environment that encourages organ-specific cell growth [24]. Bioreactors should allow nutrient-rich oxygen to be pumped with adjustable rates of flow and pressure and monitor and control the pH and temperature of the media. Moreover, mechanical stimulation is also an essential component for engineering organs of the musculoskeletal and cardiovascular systems [71]. A wide range of mechanical properties is employed in the design of bioreactors, including substrate stiffness and dynamic changes in stiffness throughout culture, pulsatile flow, and providing stretch to enhance cell maturation, alignment, and generation of force in engineered constructs [72]. Presently, there are several types of bioreactors available, with Radnoti [73] and BIOSTAT B-DCU II [74], to name a few. In addition, there has been an increase in bioreactor designs incorporating real-time monitoring to assess the status of engineered tissues. These designs may incorporate biochemical probes to assess transmural pressure changes or sampling ports to test cells viability and biochemical composition after recellularization [75,76]. The incorporation of sampling methods within bioreactor designs will keep constructs sterile, allowing for modifications in stimuli to be made while maintaining a closed system, and providing researchers with valuable feedback on cell responses throughout bioengineering. Further research is being conducted to make bioreactors that can be used to maintain the perfect milieu for growing these bioengineered tissues and organs.

For an organ to be viable for transplant, three things must be ensured: sterility of the process, structural integrity, and, lastly, patency for surgical anastomosis. Biological tissues are sterilized by gamma radiations or peracetic acid at low concentrations before the ECM is repopulated with cells[77]. Once the cells are added, antibacterial, antifungals, and other antibiotic drugs can be utilized. It is re-evaluated for integrity before the ECM is recellularized and only gets the green light for cell seeding if structural integrity is maintained. Interestingly, with the aid of endoscopy, decellularized constructs can be easily manipulated and visualized for macro and microstructure defects at the level of chambers, papillary muscle, and valves[47]. One of the most important aspects of evaluating the integrity of ECM is to check for intact coronary vasculature, which can be done by micro-optical coherence tomography [48].

Heart constructs engineered in the lab have been demonstrated to undergo cyclical muscular contraction but also have been shown to respond to drugs and exhibit electrical activity. However, electrocardiography analysis of the bioengineered hearts has shown irregular wave morphology due to loss of coupling between cardiomyocytes [78]. Therefore, it will be crucial to develop continuous monitoring of cardiac electrophysiology, function, and even vascular patency if these artificial constructs can be transplanted into patients.

Over the past decade, research in regenerative medicine has enabled us to understand better the challenges associated with developing a bioartificial heart. The first challenge was creating a biocompatible scaffold which has already been resolved with the development of various decellularization techniques, making it possible to generate an anatomically accurate and vascularized heart scaffold. With the advent of newer techniques for iPSC generation of stable karyotype, cell generation is also potentially resolved. Presently, research has to be aimed to address the challenges in reseeding the ECM scaffold. A potential solution might be the advancement in 3D-printed matrixes with embedded cells. However, decellularized ECM remains the gold standard for now as 3D-printed matrixes cannot replicate the complexity and structural integrity of the natural component of ECM.

Another potential problem is the creation of a bioreactor that can efficiently maintain the environment required for the growth of cardiac and other differentiated cells around the decellularized ECM scaffold. Constructing organs is no easy feat and involves much technical expertise. Hence, many resources are required in every step of artificially reproducing tissues and organs. Thus, even if bioengineering a heart is a possibility in the near future, it may not be financially feasible to use them for transplantation until the cost of making such constructs is lowered. Additionally, we do not know the long-term viability of such constructs. These constructs use chemicals to decellularize ECM as well as induce the conversion of adult cells into pluripotent cells. Some questions arise on how the complex network of cells and ECM would interact over the long run. The heart is a complex organ that requires a highly specialized conduction system to ensure efficient, coordinated, and purposeful contraction of the heart chambers. Any deviance may lead to fatal arrhythmia or thrombus formation. We are yet to reproduce a perfect conduction system in the lab, let alone test its long-term functionality. Furthermore, the use of induced pluripotent cells also raises the prospect of long-term tumorigenesis and malignancy. Despite rapid advances in bioengineering and artificial hearts, research and clinical trials must be conducted to determine the long-term feasibility of using these organs.

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Is a Bioengineered Heart From Recipient Tissues the Answer to the Shortage of Donors in Heart Transplantation? - Cureus

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DUBLIN--(BUSINESS WIRE)--The "Heart Failure - Pipeline Insight" clinical trials has been added to ResearchAndMarkets.com's offering.

This "Heart Failure - Pipeline Insight, 2022" report provides comprehensive insights about 90+ companies and 90+ pipeline drugs in Heart Failure pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

"Heart Failure - Pipeline Insight, 2022" report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Heart Failure pipeline landscape is provided which includes the disease overview and Heart Failure treatment guidelines.

The assessment part of the report embraces, in depth Heart Failure commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights

Heart Failure Emerging Drugs

Tirzepatide: Eli Lilly and Company

Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight. Tirzepatide is in phase 3 development for chronic weight management and heart failure with preserved ejection fraction (HFpEF). It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH). Both the FDA and EMA have accepted Eli Lilly's marketing approval applications for its type 2 diabetes treatment, tirzepatide.

Finerenone (BAY94-8862): Bayer

Finerenone (BAY 94-8862) is an investigational novel, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that has been shown to block the harmful effects of the overactivated mineralocorticoid receptor (MR) system. MR overactivation is a major driver of heart and kidney damage. Current steroidal MRAs on the market have proven to be effective in reducing cardiovascular mortality in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, they are often underutilized due to the incidence of hyperkalemia, renal dysfunction, and anti-androgenic/ progestogenic side effects.

CardiAMP Cell Therapy: BioCardia

CardiAMP Cell Therapy uses a patient's own (autologous) bone marrow cells delivered to the heart in a minimally invasive, catheter-based procedure to potentially stimulate the body's natural healing response. The CardiAMP Cell Therapy Heart Failure Trial is the first multicenter clinical trial of an autologous cell therapy to prospectively screen for cell therapeutic potency in order to improve patient outcomes. CardiAMP Cell Therapy incorporates three proprietary elements not previously utilized in investigational cardiac cell therapy, which the company believes improves the probability of success of the treatment: a pre-procedural diagnostic for patient selection, a high target dosage of cells, and a proprietary delivery system that has been shown to be safer than other intramyocardial delivery systems and more successful for enhancing cell retention.

Rexlemestrocel-L (Revascor): Mesoblast

Revascor consists of 150 million mesenchymal precursor cells (MPCs) administered by direct injection into the heart muscle in patients suffering from CHF and progressive loss of heart function. MPCs release a range of factors when triggered by specific receptor-ligand interactions within damaged tissue. Based on preclinical data, it is believed that these factors induce functional cardiac recovery by simultaneous activation of multiple pathways, including induction of endogenous vascular network formation, reduction in harmful inflammation, reduction in cardiac scarring and fibrosis, and regeneration of heart muscle through activation of tissue precursors.

BMS-986231: Bristol-Myers Squibb

Cimlanod (development codes CXL-1427 and BMS-986231) is an experimental drug for the treatment of acute decompensated heart failure. HNO gas (nitroxyl) is a chemical sibling of nitric oxide. Although nitric oxide and HNO appear to be closely related chemically, the physiological effects and biologic mechanisms of HNO and nitric oxide action are distinct. The biologic effects of HNO are mediated by direct post-translational modification of thiol residues in target proteins, including SERCA2a, phospholamban, the ryanodine receptor, and myofilament proteins in cardiomyocytes. In vitro, HNO increases the efficiency of calcium cycling and improves myofilament calcium sensitivity, which enhances myocardial contraction and relaxation. HNO also mediates peripheral vasodilation through endothelial soluble guanylate cyclase. HNO does not induce tachyphylaxis in peripheral vessels, unlike nitric oxide.

Elamipretide: Stealth BioTherapeutics

Elamipretide (MTP-131, Bendavia) is a novel tetra-peptide that targets mitochondrial dysfunction in energydepleted myocytes. Elamipretide crosses the outer membrane of the mitochondria and associates itself with cardiolipin, which is a phospholipid expressed only in the inner membrane of mitochondria. Cardiolipin has an integral role in mitochondrial stability and organization of respiratory complexes into super complexes for oxidative phosphorylation.Thus, elamipretide helps to enhance ATP synthesis in multiple organs of the body. Elamipretide has been shown to improve left ventricular ejection fraction (LVEF), LV end diastolic pressure, cardiac hypertrophy, myocardial fibrosis, and myocardial ATP synthesis in both animal models and humans.

FA relaxin: Bristol Myers Squibb

BMS-986259 is a next-generation version of Relaxin that is enabled with our technology and currently in Phase 1 clinical trials for ADHF. Relaxin, a peptide hormone, has been reported to reduce fibrosis in the multiple organs and to exert cardioprotective effects in preclinical studies. However, the therapeutic potential of Relaxin has been partially limited by its short half-life in humans. BMS-986259 has exhibited a prolonged half-life and therefore has the potential to enhance clinical benefit as a novel therapeutic for ADHF.

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For more information about this clinical trials report visit https://www.researchandmarkets.com/r/soc45u

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Global Heart Failure Pipeline Market Research Report 2022: Comprehensive Insights About 90+ Companies and 90+ Pipeline Drugs - ResearchAndMarkets.com...

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Its a symbol of love and courage. It flutters with excitement and panic. It knows when to rest and when to quicken. But, most importantly, the heart is an extraordinary machine. These doors inside your heart [the valves] have to flap open and closed 100,000 times a day, says cardiologist James Wong. If you did that to your front door it would be gone in the afternoon.

Yet, as with all complex machinery, over time the heart can develop issues. One of the more insidious problems lies in its plumbing the coronary arteries which, when blocked, cause a heart attack.

One in every 25 deaths in Australia in 2020 was due to a heart attack. Thats the equivalent of 18 deaths a day, or one every 80 minutes. Sometimes, heart attacks are sudden and brutal. Other times, people dont realise they are having one. And they are often different for women and men.

So, how do you know if you are having a heart attack? What does a massive heart attack mean? Can you test for signs? And to what extent can you prevent them?

Credit:Artwork Matt Davidson

The heart is a pump made of muscle with its own electrical circuits and plumbing. Its job is to bring oxygen and nutrients to all our organs in just the right amount. It normally beats up to 100 times a minute more when you exercise. With each beat, it squeezes to circulate blood from the lungs to the rest of body then back again. Valves keep blood flowing in the right direction, pieces of thin, strong tissue like parachute material. Its amazing how resilient they are to withstand pressure without tearing, says Wong, an associate professor of medicine, who is director of the Royal Melbourne Hospitals echocardiography laboratory.

Its the best pump that Professor Garry Jennings knows of and the most hardy. Not many pumps work for 90 years, 100,000 times a day, says Jennings, the Heart Foundations chief medical adviser.

Its a lot of responsibility for an organ the size of a fist, but it has its own electrical system to help.

Tiny electrical impulses trigger each heartbeat, beginning in the sinus node at the top of the heart before travelling, like a Mexican wave, through the hearts four chambers two atria and two ventricles with the atria contracting a fraction of a second before the ventricles to push the blood. Wong likens the sinus node to the guy that beats the drum, which the rest of the heart follows, thereby controlling the heart rate.

Researchers have found that every time the heart beats, the brain pulses in sync ever so slightly.

An electrocardiogram, or ECG, produces the pulsing graph you see on screens at hospitals (and much beloved by makers of TV dramas). It detects the hearts contractions by reading its electrical activity via electrodes on the skin.

The heart contracts automatically, but the brains autonomic nervous system regulates the strength and pace of the contractions. The brain and heart depend on each other: the brain supports the hearts pumping, and the heart keeps the brain oxygenated. In fact, researchers have found that every time the heart beats, the brain pulses in sync ever so slightly.

But to do its job, the heart relies on having a rich blood supply, which is where its plumbing comes in: the coronary arteries are the blood vessels that wrap around the heart to nourish it with oxygenated blood. A heart attack occurs when that supply is impeded, cutting off nourishment and preventing the heart from keeping up with the demands of the body. The heart has to work pretty hard, and if you cut off the blood supply to a part of the muscle then it runs into trouble, says Jennings.

A heart attack is a medical event where blood flow in the coronary arteries becomes restricted, resulting in irreversible damage to the heart muscle. Because theres no blood flow being delivered to that part of the heart muscle, that part dies, Wong says.

The extent of the damage will vary but the consequences can be devastating, leading to a life sentence of chronic heart failure, or death.

What tends to determine a heart attacks severity is the location of the artery blockage and the time taken to clear it, as these two factors will dictate how much irreversible scarring is left behind.

You might hear that someone died of a massive heart attack. Picture the coronary arteries as being made up of three major freeways then side streets, avenues and laneways. Wong explains: If the blockage happened very much downstream and one of the side streets is blocked off, were not talking about a big volume of heart [thats low on supply]. Compare that to the start of the freeway being blocked then everything downstream is going to get wiped out because the narrowing happened to be at the wrong spot.

Blocked at the start of the freeway, the heart simply cant pump the blood out to the brain and other organs, and that can result in life-threatening cardiac shock. Wong says there is a particularly bad zone for a blockage, which is the left main stem where blood vessels lead into the heart. If it blocks off, probably two-thirds of the heart will go. That is not sustainable at all.

Its estimated that more than half of people killed by a heart attack die suddenly. In other cases, a blockage can harm the hearts electrical system causing cardiac arrhythmia, which can be fatal too: the hearts rhythm goes berserk and cant pump. The heart doesnt have time to fill then it cant empty properly. So its just fluttering instead of a regular beat in and out, Jennings says.

This can then lead to cardiac arrest, which is not the same as a heart attack, although heart attack is a common cause of cardiac arrest. You might think of a heart attack as more of a plumbing-related issue caused by a blockage while cardiac arrest is due to a malfunctioning of the hearts electrical system, prompting the heart to beat erratically thats where defibrillators come in, as an arrest is treated with electric shock.

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A heart attack is usually a result of coronary heart disease (also called ischaemic heart disease or coronary artery disease), an umbrella term for a range of conditions that can affect the heart when blood flow in the coronary arteries is compromised.

For some people, a heart attack is the first time a person realises they have the disease. Its Australias biggest killer overall; the leading cause of death in men, and, in women, it is the second-leading cause after dementia. Heart attacks are responsible for two-fifths of all coronary heart disease deaths.

Another important distinction: coronary heart disease is just one form of heart disease. Heart disease and cardiovascular disease are the same thing and are broad terms that include any disease of the heart or blood vessels, such as stroke and congenital heart conditions.

Angina, meanwhile, is a short-lived chest pain caused by blood flow issues its a sign of coronary heart disease but less intense than heart attack pain.

Most of us probably have an image in our heads of someone clutching their chest and collapsing. Wong says the textbooks dont always reflect real life but theyre the best place to start. People often get chest pains across the front of the chest, which radiate to their jaw or down their left arm. Its also associated with some breathlessness, sweatiness or nausea, he says.

Its not always like that, though. Women, for example, are less likely to have chest pains, more likely to have breathlessness, excessive sweating, dizziness or neck and back pain. One day in 2020, disability support worker Kath Moorby felt discomfort in her right shoulder and hand followed by tingling in her arms and fingers. Then she felt hot, clammy and sweaty. There was no chest pain, just a heaviness.

It was a surreal moment. Really? Im 44 and Im having a heart attack?

Paramedics eventually determined she was having a heart attack. It was a surreal moment, she recalls. Really? Im 44 and Im having a heart attack?

Moorby had two stents implanted. She says the effect was instant: the pressure in her upper-body reduced and her blood could flow freely again. They said I had a 20 per cent chance of surviving had I not made it to hospital when I did, she recalls.

Other people experience tightness rather than crushing pain.

People usually become cold, white and clammy, Jennings says. But symptoms can be variable.

Andrew van Vloten, a 53-year-old Victorian park ranger, had his first heart attack in 2014. With a family history of heart disease, he says, looking back, there had been signs for months that something was off: he felt occasional chest and jaw pain, especially when exercising, as well as shortness of breath. One day at work, the chest pains returned and wouldnt subside. It was getting quite intense, the pressure right on the centre of my chest I then started to get pins and needles in my fingers and toes. It was full-on, van Vloten says.

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He had a stent put in that day.

To avoid a repeat, he set about exercising more and ate less saturated fat, red meat and processed food. Six months down the track, I felt as fit as Id been in 10 years.

Its why he was so shocked when he had a second heart attack in 2020. This time he had no symptoms in the lead-up other than feeling a bit unwell. Then, as he was loading up timber into a ute, he was hit by nausea, breathlessness and chest pains. It just came on really quickly and intensely, he says. Everything started coming back to me.

It can be easy to mix up heart attack symptoms with heartburn, oesophageal spasms or angina. If the pain lasts more than 10 minutes, its worth seeking urgent medical attention. Its a heart attack when an artery blocks off and nothing a patient does makes it better, Jennings says.

Sometimes a heart attack can happen when the heart is under more pressure, such as during exercise or even following a big fright.Other times, theres no particular exertion. To complicate matters, one-sixth of people experience silent heart attacks no symptoms. This is more likely in people who have diabetes because their nerve endings can be blunted.

Sometimes we do ECGs on people for insurance purposes, and we find that theyve had an old heart attack somewhere along the way, Wong says. Its like if you damaged any part of you, you would scar, with scar tissue replacing the damaged tissue. The same thing happens in the heart.

Credit:Artwork Getty/Marija Ercegovac

They might seem to come out of the blue but a heart attack often reflects a process that has been going on throughout a persons life. Atherosclerosis is the narrowing and hardening of arteries. It starts in adolescence, if not before, brought on by a build-up of plaque (made of cholesterol and other substances) on the inner wall of the arteries. Once it gets underneath that inner lining of the vessel wall, its really hard to get out again, Wong says, so its almost like a one-way street.

By the time the guy whos been doing absolutely nothing, sitting all day, comes to you with chest pain, thats really late.

You wont be aware of much of the gradual narrowing because the body manages fine until it reaches a particular point. Its only once a coronary artery narrows by between 60 and 70 per cent that blood flow falls off noticeably and someone might begin to tire more easily or feel bursts of chest discomfort. That partly explains why some people feel great one week and dont feel good the next, Wong says.

This is also when coronary heart disease is in full swing. The artery wall becomes more unstable, so a blob of plaque can crack off and lead to clotting. This is the most common way a blockage happens before a heart attack but there are others. Sometimes, heart attacks occur in people without significantly clogged arteries, Wong says. There might be a spasm of the muscle lining in the artery that causes it to clamp down or, in rare cases (about 2 per cent of heart attacks) mainly in women, there can be a tear in the inner artery wall that peels off and blocks circulation (this is called spontaneous coronary artery dissection, or SCAD). Or plaque might simply be unstable, slough off and clog an artery more common in smokers.

Credit:Artwork Stephen Kiprillis

If someones exercise capacity is consistently worsening, it can be a sign their arteries are narrowing dangerously. It means when the heart is being asked to do more work, its not getting enough blood flow to it, Wong says. Maybe you used to be fine walking five kilometres, three the next month, then two; or walking room to room becomes too much. It will be unrelenting, its not something that would come and go away, Wong says. People need to be honest with themselves by the time the guy whos been doing absolutely nothing, sitting all day, comes to you with chest pain, thats really late. The artery is likely to be quite narrowed.

There are various tests you can do. As a first step, Wong advises his patients to try an online calculator such as cvdcalculator.com, where you punch in your data (for example, age, smoking status, cholesterol levels) to get an understanding of your risk and how making small lifestyle changes can make a big difference.

You dont have to have symptoms of heart disease to get a heart health check. Any patient over 30 is eligible.

A basic heart health check, usually done by a GP, can determine risk levels and help work out whether you are harbouring artery disease. You dont have to have symptoms of heart disease to get a heart health check. Any patient over 30 is eligible. Its covered by Medicare once in a 12-month period and is recommended for adults aged 45 and over, or Aboriginal and Torres Strait Islander people aged 30 and over.

A patient might have further tests if its appropriate, such as a calcium-score CT scan (more calcium deposits in the coronary arteries means theres a higher chance theyre narrowed) or an ECG or a cardiac stress test, which examines how the heart responds to exercise. These tests can cost a few hundred dollars, which Medicare generally covers only if someone has heart disease symptoms.

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To check to what extent someones arteries have narrowed, a coronary angiogram involves injecting dye into the hearts blood vessels, which is picked up using an X-ray machine.

Depending on the patient, they might be prescribed medication to treat cholesterol, blood pressure or clotting. Or a doctor might recommend inserting a stent or doing coronary artery bypass surgery to redirect blood flow by grafting a healthy blood vessel.

Its difficult not to be alarmed by the stories of fit, healthy people who collapse suddenly with a heart attack. Wong says these are rare events often caused by inherited, underlying heart disease. But anyone who has concerns can talk to their doctor about tests that will help them ascertain their hearts health, and what level of physical activity is safe for them.

Twice as many men are admitted to hospital with a heart attack compared to women, although the disparity in deaths is slimmer: in 2020, 2800 women and 3700 Australian men. This is, in large part, because of differences between how these events present in the two sexes studies having long shown that many women have their symptoms dismissed or misdiagnosed.

The average age of a first heart attack is 72 for women about 10 years older than men.

The average age of a first heart attack is 72 for women about 10 years older than men and theyre more likely to have a spontaneous artery tear, a blockage in a small coronary blood vessel or a mini heart attack where a smaller artery doesnt open up properly, despite no significant narrowing. The biology that causes heart attacks can be a bit more varied in women than men, Jennings says.

Women with a history of pre-eclampsia or gestational diabetes during pregnancy or endometriosis also have a higher risk of coronary heart disease.

There are some inequalities in who suffers most from heart attacks. The rate of hospitalisations and deaths is about 1.5 times higher for people in remote or lower socioeconomic areas, the Australian Institute of Health and Welfare reports. For Indigenous Australians, the rate is double that of non-Indigenous Australians.

People with diabetes are roughly four times more likely to have a heart attack. And mental health is important for the heart: depression can increase your risk of developing coronary heart disease just as much as smoking and high blood pressure.

Phone triple zero. While you wait for an ambulance, it helps to focus on breathing steadily to try to calm yourself. With any heart attack, Wong says the key is to have as short a door-to-needle time as possible. Normally, paramedics alert a hospital of a heart attack patient before arrival.

Sometimes theyll be given clot-dissolving medication, or a catheter tube is threaded up the arm or leg and a tiny balloon widens the narrowed coronary artery to leave behind a wire mesh, called a stent, to prop it open. Every minute counts in doing that, Jennings says, because the longer you wait, the more the heart muscle cells will be dying.

The part of the heart not affected by the blockage will keep working to contract, but it will be strained and the damage can spread. There is a risk of chronic heart failure, where the hearts pump mechanism is weakened long-term. They could be fine sitting or lying down but when they start walking up a hill, they cant do it. They have a limit and their lifestyle has to be adjusted to what the heart allows them to do, Wong explains. In severe heart failure cases, an artificial pacemaker or organ transplant may be needed.

Weve seen some horrendous things that could have been dealt with a lot sooner.

Treatment involves looking after the other arteries because you cant afford to lose any more heart muscle with another heart attack.If we get them from their home to hospital within two to three hours then we have a very high chance of salvaging their heart muscle and keeping them alive. If its five to six hours after the onset of the heart attack, even if you unblock the artery, the amount thats salvaged is much less, says Wong.

There have been too many preventable heart attack deaths from patients who stayed away from hospital during the pandemic, Wong says. Weve seen some horrendous things that could have been dealt with a lot sooner, he says. Having ambulances ramped outside emergency rooms is a particular concern in heart attack cases.

When treatment is swift, you can go on to lead a normal life, with medication and lifestyle adjustments to help keep your arteries open. Still, its estimated that about 20 per cent of heart attack patients will be hospitalised with a second one within five years, a reality that Wong says can make people feel very anxious.

Its why cardiac rehabilitation is so important as it involves structured physical activity and education on lifestyle and medicines, Jennings says, urging people to speak to their doctor about enrolling in a program or use the Heart Foundations directory to find one.

The heart does age and wear out eventually, Wong says. Sometimes I have to say to patients, Its more a case of youve had too many birthdays. That said, a heart attack is eminently preventable, Jennings says, particularly under the age of 80. The goal is to slow the rate at which the coronary arteries are narrowing and stiffening.

First, its good to understand what we can control. We cant change our age nor our genetics, both of which are unavoidable factors in our risk of heart disease. Some people can do all the wrong things [for their health] and never have a heart problem. Other people barely infringe and suffer from heart disease, says Jennings.

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Some people have a family history of heart disease. Wong starts to treat such patients about five years before their close relative who had heart trouble started having issues. Some people might have naturally high cholesterol (called familial hypercholesterolemia). Here, heart complications tend to occur in someones 20s.

Health issues such as high cholesterol or blood pressure have effective medications. But whatever your genetic background, youll still be better off with a better lifestyle, so never give up, Jennings says. Poor nutrition, low physical activity, drinking alcohol, smoking and being overweight: these are all major risk factors that can be improved. A 2019 study of more than 26,000 people aged over 18 found that a healthy lifestyle was linked to a 44 per cent lower risk of coronary heart disease.

This might sound a bit airy-fairy, but I say thank you to my heart every day. I am in absolute awe of my heart.

Sometimes people become scared of putting pressure on their heart with exercise but Jennings urges people to ditch the fear. Theres nothing better you can do for your heart than being physically active, he says. Sensible exercise, where people build up a program and get fit, is one of the healthiest things.

The Mediterranean diet remains the gold standard for a healthy heart, he says, and instead of focusing on food components, such as fat and cholesterol, there is increasing emphasis on healthy food combinations so, lots of fruit and vegetables, olive oil, fish and chicken because people eat food, not polyunsaturated fat .

Kath Moorby had many risk factors, from family history to years of weight struggles. Before her heart attack she had lost 100 kilograms but her diet remained unhealthy, and she was smoking 50 cigarettes a day. What you do in your younger years comes back to bite you on the bum, Moorby says. Today, she eats better, walks, doesnt drink and no longer smokes.

While coronary heart disease kills more Australians than any cancer (lung cancer is the fourth-leading cause of death in men and women), Jennings observes that cancer tends to be more feared in society, not least because people fade away in front of us, whereas with a heart attack [often] theyre just gone [suddenly].

He says there is a degree of unfair blame that is heaped on heart disease patients too. Its not necessarily their fault if theyre overweight or have undetected risk factors. We just need to help them a bit more, he says.

Andrew van Vloten, who had two heart attacks, urges people to learn about their bodies and their limits and take any heart disease risk factors seriously by visiting a doctor. Today, hes a proud 10-kilometre race finisher, and he connects with his heart through meditation. This might sound a bit airy-fairy, but I say thank you to my heart every day, van Vloten says. I am in absolute awe of my heart, the function it does and what its capable of doing.

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Whats a heart attack? How can you tell if youre on the edge of one? - Sydney Morning Herald

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Neurosurgeons, researchers and engineers have come together to make it possible for a man who's a quadriplegic to drive a car using his brain.

On a track in Colorado Springs, racing thoughts and motor function have deeper meaning.

Quadriplegic German Aldana Zuniga lost movement after a car accident when he was 16 years old.

Now, he's the first patient to drive with his brain.

He can pull out of pit row, punch the throttle and speed away using only his mind and technology.

It all started with a question in 2013. Spinal cord neurosurgeon Dr. Scott Falci wondered, Could you modify a race car so people with spinal cord injuries can drive it?

"A large portion of this population that I was dealing with had a love affair for automobiles, cars, motor sports," Dr. Falci said. "I want to get spinal cord injured patients and just mobility-impaired patients in a race car where they can drive it themselves and just for the fun and the motivation and the inspiration that it would provide."

It could also serve as a real time lab. Engineers developed a modified driving system, using data from rides to improve the tech.

States away the Miami Project to end paralysis had their own research question: Could an FDA approved brain device for Parkinsons patients work for quadriplegics?

This is where Zuniga comes in. Miami Project doctors implanted that brain device in him and made a glove that connects with it.

Biomedical engineer Kevin Davis is part of the team.

Whenever hes thinking about moving his arm, we can detect a difference in the neural activity and that difference is what allows us to control external devices," Davis said.

The scientists joined forces with a new goal to combine both technologies.

"If we could harness the computational power of the brain, we could really take this quite far," Dr. Falci said.

Mind driving works like this: Zuniga forms a thought, like "open or look forward."

In the brain, that thought is a special signal with a unique electrical fingerprint. A part on the implanted device on top of his brain detects that signal and feeds it to computers in the car. Those computers are programmed to understand open and look forward and push the throttle and drive the car away.

Engineers swapped software code from Colorado to Florida while Zuniga drove a simulator for over a year. When it the time came for the real car:

"Its not even close, its totally different," Zuniga said. "You see the track, how big it is, the noise of the car, the heat of it."

"Over here when that is blue, hes thinking throttle off, when he goes green hes thinking throttle on, and youll see the numbers go up," Dr. Harry Direen said.

It's eight laps total, 850 horsepower, one quick water break.

Its the first time Zuniga has ever driven. He became a quadriplegic before he could get a drivers license.

"Once youre on the road, you feel the rush, the adrenaline," Zuniga said. "The track feels so short. I feel good, I feel fantastic, very happy."

The data from the track lab will go to improve the next ride, plus practical applications like controlling an electric wheelchair or an robotic prosthetic.

Dr. Falci is also researching how to restore spinal cord function with stem cells. It could bring back movement and feeling in the body.

"Regenerating the spinal cord, because that's the healthiest of all conditions," Dr. Falci said. "The more we can do for them or help them do on their own, the independence gained and the quality of life just goes up dramatically."

The road ahead for full restoration is a long one.

Dr. Falci has already spent 29 years working on it, but hes not gassed.

No matter how many more trips around the track it may take, theres one willing patient ready to propel forward.

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Vertigo refers to a false sense of motion that can occur regardless of whether a person is moving. It is not a condition in itself but a possible symptom of several medical conditions.

Physical therapy may help a person reduce or eliminate vertigo. However, they should first speak with a doctor who can determine the underlying cause.

Once the doctor has confirmed a diagnosis, they may recommend physical therapy to help improve the persons symptoms.

This article explains how physical therapy can help people who experience vertigo. It also looks at exercises that a person can try at home and explains how to find a physical therapist.

Vertigo refers to a sensation of motion that is unrelated to the persons actions, and it typically presents as a spinning sensation. It may sometimes make a person feel as though their surroundings are spinning around them.

Vertigo is a symptom of other issues. However, it can also occur alongside or lead to other symptoms, such as balance issues, nausea, and motion sickness.

There are two types of vertigo: peripheral and central.

Peripheral vertigo accounts for about 80% of cases and is often the result of benign paroxysmal positional vertigo (BPPV).

The remaining 20% of cases are central vertigo, which results from lesions on the brain stem or another issue affecting the brain.

Both multiple sclerosis (MS) and migraine can cause central vertigo.

BPPV occurs when calcium carbonate crystals in the ear, known as canaliths, come loose and move into one of the fluid filled canals.

It is the most common cause of peripheral vertigo.

These crystals interfere with the normal movement of fluid in the canals. The purpose of the fluid is to sense movement, but disturbances can cause it to send false signals to the brain.

This tricks the brain into thinking that a person is moving, even if they are not. The false signal contradicts what the other ear senses and what the eyes are seeing. This conflicting information causes a spinning sensation, known as vertigo.

Physical therapy can help with vertigo. The most suitable exercises may vary depending on the type of vertigo. A person should make sure that they have the correct diagnosis before seeking physical therapy or trying exercises at home.

Healthcare professionals may use a form of physical therapy called vestibular rehabilitation therapy (VRT) to help with vertigo. VRT may help people with vertigo resulting from BPPV, head injuries, central nervous system lesions, and undefined causes.

However, this type of therapy might not work for all causes of vertigo. The aim of VRT is to help a person anticipate vertigo from known triggers and take action to prevent it from occurring. As a result, people who experience sporadic, unpredictable incidents may not benefit from VRT.

The symptoms of vertigo may either reduce or worsen during VRT exercises.

Sometimes, worsening symptoms may be due to unnecessary overuse of the exercises on a good day, which can cause fatigue, resulting in increased symptoms.

Even if the exercises seem to have resolved the symptoms of vertigo, a person can experience a relapse of symptoms at a later time.

Some exercises for vertigo may be easy for people to do at home. However, it is important to determine the cause of vertigo before beginning any therapy to treat the symptoms.

A person should also follow all exercise recommendations from a doctor or therapist. These professionals can explain each exercise in more detail and provide guidance on what to expect and when to stop.

This section explains how to perform two canalith repositioning exercises that may help alleviate vertigo.

Learn more about exercises for vertigo.

This common exercise is particularly effective in treating BPPV.

A person can perform the Epley maneuver by following these steps:

A person should then repeat the same movement on the opposite side in other words, facing the right at the beginning. They can do this up to three times per day until they no longer experience vertigo for at least 24 hours.

Learn more about the Epley maneuver with a step-by-step video guide.

This is a similar exercise that involves alternating between sitting and lying positions.

To perform Brandt-Daroff exercises, a person should:

Learn more about Brandt-Daroff exercises with a step-by-step video guide.

A person can ask a healthcare professional for their recommendations regarding physical therapists in the area. Not all therapists will have the same level of experience, and some may not know how to treat all causes of vertigo.

A person who needs help finding a physical therapist can use the Academy of Neurologic Physical Therapys website to find a local professional in their area.

The Vestibular Disorders Association also offers a resource that can help a person find physical therapists in their area.

The costs of physical therapy can vary, but health insurance may cover some or all of the costs. A person with a health insurance plan should contact their provider to determine how much of each session it will cover.

Those without insurance should talk with a healthcare professional, who may be able to provide information on local resources that can help cover the costs.

Learn more about Medicare and Medicaid.

Vertigo treatments can vary depending on the exact underlying cause. Once a person treats the underlying cause, the symptom of vertigo should resolve.

Other treatments that can help treat some causes of vertigo include:

Learn more about home remedies for vertigo.

With physical therapy and other effective treatments, most people should see their vertigo improve. A doctor can address any underlying conditions responsible for the vertigo.

However, a person may still experience some vertigo in the future. For example, about 50% of people will experience a relapse in BPPV within 5 years. In addition, about one-third of people experiencing vertigo from anxiety will still experience symptoms after 1 year.

Vertigo is a symptom associated with several different conditions. It occurs when a person experiences spinning and dizziness or feels as though their surroundings are moving around them.

Physical therapy can help improve a persons vertigo. A person should speak with a doctor before starting any new program to make sure that they receive effective treatment for the underlying condition.

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Physical therapy for vertigo: Exercises, benefits, and more - Medical News Today

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Danielle Roy says multiple sclerosis has turned her into a prisoner of her own body, which is why she is seeking a procedure that is only available outside of Canada and she needs the publics help to afford it.

The autoimmune disorder has slowly taken away her ability to walk and hold objects, leaving her wheelchair-bound after years of fighting to keep what mobility she has left. Roy said she is not giving up and is setting her sights on a stem-cell procedure that is still in the experimental phase in Canada but is being used in other countries to treat autoimmune disorders.

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Danielle Roy is reaching out to the public to help her pay for an experimental stem-cell procedure in Mexico to halt the progression of her MS.

However, the nearest clinic is in Mexico, and it is going to cost her around $84,000. Neither Roy nor her caregiver and friend Evan Anthony have that kind of money, so they launched a campaign on GoFundMe to raise funds before applying for loans.

Roy said she knows asking for that much money is a lofty goal, but she has reached a point where she cannot tolerate her MS any longer.

"Im going to be bedridden soon. Im lucky I still have a lot of upper-body strength to get out of bed and into my chair," she said. "Really, I dont want to have to face another winter with this. For some reason, it makes my MS worse, and things really started going downhill after this winter."

What Roy is hoping to undergo is known as hematopoietic stem cell transplantation (HSCT). According to the medical information website Medscape.com, this involves injecting hematopoietic stem cells into the veins to re-establish blood-cell production in patients whose bone marrow or immune system is damaged or defective. This technique has been used with increasing frequency over the past 50 years to treat numerous malignant and non-malignant diseases.

Cells for HSCT may be obtained from the patient or from another person, such as a sibling or unrelated donor or an identical twin. Cell sources include bone marrow, peripheral blood and umbilical cord blood. Roy said the stem cells from her own body will be used.

According to the MS Society of Canada, the disease attacks the myelin, the protective covering of the brain and spinal cord, causing inflammation and often damaging the myelin in patches. When this happens, the usual flow of nerve impulses along nerve fibres (axons) is interrupted or distorted.

Depending on the type and the persons overall health, the result may be a wide variety of symptoms, depending on which part or parts of the central nervous system are affected. This includes numbness, loss of muscle control, paralysis, difficulty speaking, dizziness, loss of bowel and bladder control, difficulty swallowing and tremors. Not all people with MS will experience all symptoms, and often the symptoms will improve during periods of remission.

There are various ways to manage symptoms, ranging from drug treatments to non-medicinal strategies such as physiotherapy, occupational therapy, exercise programs and alternative and complementary treatments.

Roy was diagnosed in 2005 at the age of 19 and slowly lost mobility until she required an electric wheelchair. In 2010, she and her family ran a penny collection campaign to pay for a treatment anchored in the theory MS was caused by blocked neck veins that needed to be opened with angioplasty. At the time, such treatments were only available overseas.

Since then, it has been a series of ups and downs with several medications and therapies. The problem with those, she said, is they only slow down progression or manage symptoms for a time before they become worse.

The psychological effects have been just as devastating.

"I used to be so active, a cheerleader, a runner," she said. "Now, I feel a little jealous when I see someone holding a cup of coffee. This is my life, and Ill try anything to save it."

The hope is this treatment will stop the progression of MS and allow her body to heal itself and regain at least some of her mobility.

"Other treatments slow things down or do damage control, but with HSCT, it stops progression entirely," Anthony said. "Its not a treatment, but its hard to not call it a treatment. You can get it more than one time, but it is really meant to be a procedure done once."

Anthony said he can take out a loan to help pay for some of the procedure, but not for more than $84,000, which is why they are once again reaching out to the public to help Roy.

To donate, visit gofund.me/f3b0eaf8.

kmckinley@brandonsun.com

Twitter: @karenleighmcki1

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Astrocytes make up almost half of the mammalian brain cells. They are called glial cells because scientists originally thought that these starlight-shaped structures serve as nerve glue.

Research suggests that these cells control the growth of axons, or the neuronal projections that carry electrical impulses.

However, scientists still considered astrocytes to be supporting actors behind neurons, which are the primary cells of the brain and nervous system.

Now, scientists at Tufts University in Massachusetts and other institutions realize that astrocytes may execute a significantly greater performance in brain activity.

Dr. Moritz Armbruster, a research assistant professor of neuroscience at Tufts, led a team of researchers in harnessing novel technology to study astrocyte-neuron exchanges.

To their surprise, the scientists observed electrical activity in astrocyte processes within mouse brain tissue. They reported: This represents a novel class of subcellular astrocyte membrane dynamics and a new form of astrocyteneuron interaction.

Dr. Armbruster and his fellow authors published their findings in Nature Neuroscience.

Using innovative tools, the Tufts team developed a technique to detect and observe electrical activity in brain cell interactions. These properties could not be seen before now.

Dr. Chris Dulla, corresponding author of the study, is an associate professor of neuroscience at the Tufts University School of Medicine and Graduate School of Biomedical Sciences. He explained that he and his colleagues []use viruses to express fluorescent proteins in the mouse brain, and thats what lets us measure this activity.

In an interview with Medical News Today, he elaborated:

[W]e had other experiments that made us think that this new type of activity must be happening in astrocytes. We just didnt have a way to show it[] So, we developed these new techniques to image the activity of the astrocytes and, using them, we showed that this thing that we thought must be happening actually was happening.

Neurotransmitters are chemical messengers that facilitate the transfer of electrical signals between neurons and support the blood-brain barrier. Scientists have long understood that astrocytes control these substances to support neuronal health.

This study breaks ground in showing that neurons release potassium ions, which change the astrocytes electrical activity. This modulation affects how the astrocytes control neurotransmitters.

Until now, scientists could not image potassium activity in the brain.

Neurons and astrocytes talk with each other in a way that has not been known about before, Dr. Dulla said.

Dr. Dulla maintains that human brain cells work the same way as mouse tissue. He said that mouse and human brain cells use the same proteins and molecules involved in brain activity.

Besides, using human tissue samples presents ethical challenges, Dr. Dulla noted: [We] have to be really careful and judicious [] with the experiments we design, and [we] dont get a chance to see [human tissue] samples like [we] can do with mice.

However, the professor shared that extensive databases give [scientists] a chance to just access human brain tissue without doing an experiment [themselves], but just getting the data that someone else has already done.

This wealth of information further demonstrates similarities between human and mouse cells and lets researchers deduce that the same processes are happening in each. The main difference is that human cells are larger and more abundant.

He also pointed out that the study highlights a bidirectional relationship between these brain cells, as astrocytes influence the neurons as well.

These findings about astrocyte-neuron interactions open a new world of questions regarding brain pathology, memory, and learning.

MNT also discussed this study with Dr. Santosh Kesari, who was not involved in this research. He is a neurologist at Providence Saint Johns Health Center in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California.

Dr. Kesari said that this study confirms earlier research.

[T]his is one of many studies thats showing increasingly, how astrocytes and neurons interact, how they affect each other and then connecting the dots to how that affects brain function behavior, memory, seizures, dementia, and even in the context of brain tumors, all these cells interact. Dr. Santosh Kesari

Most medication development for brain disorders currently targets neurons. Dr. Kesari agreed that this study might shine light on a new path.

Maybe we should really be understanding the astrocyte side of things to develop drugs that may impact brain health by looking at that astrocytic role in brain disorders, he said.

The ability to image cell processes, as in this study, makes it possible to explore other activities within the brain as well.

The researchers are also screening existing drugs in hopes of manipulating astrocyte-neuron processes. Scientists could come close to repairing brain injuries or helping people increase their learning capacity if this proves successful.

They are also making their tools available to other labs to explore more areas of interest, such as breathing, headache, and many other neurological disorders.

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Researchers find new function performed by almost half of brain cells - Medical News Today

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A Texas family said they faced a fight for their childs life after their daughter's health plan provider denied coverage of a medication known as the most expensive drug in the world.

The family said doctors told them the one-time infusion that costs millions of dollars was their daughters best hope.

Read on to learn more about their story and how an "army" of strangers stepped in.

At 4-months old, every move Aniya Porter makes is a miracle to her parents.

Aniya Porter was born with a rare genetic disease called spinal muscular atrophy or SMA.

You go day-by-day. Is my daughter going to stop breathing? Is she going to stop attempting to stand up? Is she going to stop putting her head up? Will Porter said.

Aniya was born with a rare genetic disease called spinal muscular atrophy or SMA.

SMA progressively kills motor neurons, the nerve cells in the brain stem and spinal cord that control essential functions like talking, walking, swallowing and breathing.

We live every day wondering and hoping that nothing else happens to her, that she doesn't lose any more of her motor neurons, said Hailey Weihs, Aniyas mother.

There is treatment.

In 2019, the FDA approved a drug called Zolgensma which carries a price tag of $2.1 million. The one-time gene therapy, given through an IV, is designed to replace the function of a missing or non-working SMN1 gene in a patient to stop the progression of SMA preserving motor neurons before theyre gone.

It doesn't give back what she has already lost. That's why it's so time-sensitive, explained Weihs.

When Aniyas doctor prescribed Zolgensma, Weihs and Porter said their daughters insurance, a Medicaid provider in Texas, denied coverage of the drug.

She got the denial from her insurance and that was devastating for us, said Weihs.

As they appealed, they said Aniya started to show signs she may lose control of her muscles.

She started to stop having reflexes in her legs and then her tongue started twitching, said Porter.

Racing against time, Weihs connected with other families of kids with SMA and a lawyer who agreed to represent Aniya for free.

Aniyas attorney, Eamon Kelly, told NBC 5 Responds, All the doctors agree that Aniya Porter should receive this treatment.

Kelly, who is based in Chicago, said Aniya is the seventh child with SMA hes represented in insurance coverage battles.

In Aniyas case, he said the health plan provider said the treatment was not medically necessary because doctors believe Aniya has four copies of the SMN2 gene, also known as a backup gene, which can indicate a milder illness.

Kelly argued backup genes, along with other available therapies, would not be enough to keep Aniya from losing muscle function. However, he said cutting-edge gene therapy could help.

We have a treatment that will take a little girl that is going to have a degenerative disease that threatens her life, that will put her in a wheelchair and as long as we get it to her before she's two years old and before she loses her motor neurons, she'll walk, she'll dance, she'll live a full life. Its like science fiction, Kelly said.

The first child with SMA Kelly represented is Maisie Forrest, who received Zolgensma in 2019 when she was 20 months old.

Ciji Green, Maisies mom, said Maisie was on a ventilator 22 hours a day before getting the drug.

We met with her pulmonologist and I just wept, Green recalled. I told him she's not going to make it to two and he didn't offer any words of hope because he knew Maisie was on the decline as well.

Maisie is now 4 years old.

She touches my face and it's absolutely beautiful, said Green.

Maisie is playing, talking and crawling.

Something that I have now that I didn't have was hope, hope that I will get to see her continue to meet milestones that she was never supposed to meet, Green added.

Maisies mom and a team of volunteers known as Maisies Army introduced Aniyas parents to Eamon Kelly. Last month, Kelly represented Aniya at a Medicaid State Fair Hearing.

Aniyas family requested the hearing from Texas Health and Human Services.

A week after the hearing and a few days after NBC 5 reached out to Aniyas health plan provider, Superior HealthPlan, Superior told Aniyas family Zolgensma would be covered for Aniya.

We have fought for four months. Those have been the hardest four months of our lives, said Weihs.

On April 27, Aniyas family made the trip from their home in Abilene to Cook Childrens Medical Center in Fort Worth where Aniya received the drug.

She's going to sit up on her own, she is going to walk one day, she's going to feed herself with a spoon, she's going to walk down and she's going to get her diploma, Weihs said.

NBC 5 Responds reached out to Superior HealthPlan by phone and email. We didnt hear back.

We asked Texas Health and Human Services about options for families denied coverage for Zolgensma.

It told us, in part, Medicaid covers medically necessary services including medications, and those services are delivered through managed care organizations. If the prior authorization is denied, the provider or the member can appeal the decision and MCOs have flexibility to make medically necessary decisions. Members also have the right to access the State Fair Hearing process with or without an External Medical Review (EMR). The EMR is conducted by a third-party Independent Review Organization.

It also shared, Medicaid covers alternative therapies for spinal muscular atrophy treatment, including Spinraza (nusinersen) and Evrysdi (risdiplam). Also, some manufacturers offer patient assistance programs.

A spokesperson for Novartis, which makes Zolgensma, told NBC 5, in part, Zolgensma (onasemnogene abeparvovec) is a transformative and highly innovative gene therapy for a devastating, progressive genetic disease. This one-time gene therapy is priced based on the value it provides to patients, caregivers and health systems.

It also said, Novartis is working in partnership with governments and health care systems worldwide to identify and define new sustainable access models.

Aniyas parents said she will still see a doctor and be monitored after getting the gene therapy treatment. Theyre hopeful about her prognosis.

We just knew we couldnt give up, Weihs said.

Weihs tells NBC 5 Responds the family is now focused on helping other kids get access to a drug they believe is priceless.

I don't care how expensive it is. It's a child's life. Every baby deserves a chance, said Porter.

Novartis said more than 1,800 patients have been treated with Zolgensma worldwide.

Texas newborn screening program began screening for SMA last June. The states health and human services website reports SMA is among the leading genetic causes of death among infants and toddlers.

NBC 5 Responds is committed to researching your concerns and recovering your money. Our goal is to get you answers and, if possible, solutions and a resolution. Call us at 844-5RESPND (844-573-7763) orfill out our customer complaint form.

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Texas Family Fights to Access $2.1 Million Treatment for Baby - NBC 5 Dallas-Fort Worth

Spinal Cord Stem Cells Comments Off on Texas Family Fights to Access $2.1 Million Treatment for Baby – NBC 5 Dallas-Fort Worth | May 13th, 2022

A recent study appearing in the journaleClinical Medicinesuggests that severe COVID-19 may be associated with persistent cognitive deficits, equivalent to a decline of 10 IQ points. In this study, severe COVID-19 was defined as COVID-19 that required hospitalization and critical care.

These cognitive deficits persisted until at least 6 months after contracting the SARS-CoV-2 infection, with a gradual improvement, if any, in these cognitive symptoms. These results underscore the importance of longer-term support for patients who have recovered from severe COVID-19.

According to official data from 2020, which is the same year that this study drew its data from, about 4 in 10 adults over the age of 18 are at risk of developing severe COVID-19 in the United States.

A significant minority of individuals with a SARS-CoV-2 infection experience persistent cognitive symptoms following the initial 4 weeks after the onset of COVID-19 symptoms. Some of the common cognitive symptoms include problems with concentration, brain fog, memory, and executive function.

Although persistent cognitive symptoms are also observed in individuals with mild COVID-19, such deficits in cognitive function are more prevalent in individuals with severe COVID-19. Previous studies suggest that 36%76% of individuals with severe acute COVID-19 show cognitive deficits 6 months after illness onset.

However, further research is needed to understand the specific aspects of cognitive function that are affected after severe COVID-19 and the factors that predict these cognitive symptoms.

Previous studies characterizing persistent cognitive symptoms in COVID-19 patients have relied on self-reports, which are susceptible to bias. Other studies have used pen-and-paper neuropsychological tests to assess cognitive function.

However, these tests do not possess the sensitivity to detect small changes in cognitive function or distinguish the various domains or aspects of cognitive function impacted by a SARS-CoV-2 infection.

To address these concerns, the authors of the present study used computerized cognitive tests to objectively characterize specific domains of cognitive function impacted after severe acute COVID-19. These computerized tests also allowed the researchers to assess the magnitude of these cognitive deficits.

Individuals with COVID-19 also experience persistent mental health symptoms such as anxiety, depression, fatigue, and post-traumatic stress disorder (PTSD), which could contribute to the deficits in cognitive function.

Another objective of the present study was to determine whether these mental health symptoms mediate the persistent cognitive deficits in COVID-19 patients.

The present study involved 46 patients who were previously hospitalized for severe COVID-19 and received critical care in Addenbrookes Hospital in Cambridge, England. The former COVID-19 patients completed a series of computerized cognitive tests during a return visit to the hospital, an average of 6 months after the onset of the illness.

The performance of the 46 participants on the cognitive tests was compared with that of 460 individuals in the control group. The individuals in the control group were not hospitalized for COVID-19 and were matched for age, sex, and education levels. The researchers also used self-reports to assess symptoms of anxiety, depression, and PTSD.

The researchers found that the COVID-19 patients had a lower score and a slower response time in the cognitive tests than the matched controls. People who had COVID-19 showed more pronounced deficits in specific domains of cognition, including processing speed, attention, memory, reasoning, and planning.

Notably, the deficits in cognitive function in the COVID-19 survivors were not associated with mental health symptoms present at the time of the cognitive testing, such as depression, anxiety, and PTSD.

Instead, the performance in the cognitive tests was correlated with the severity of acute illness. For instance, cognitive deficits were more pronounced in individuals who required mechanical ventilation.

The researchers then compared the performance of COVID-19 survivors with over 66,000 individuals from the general population.

The magnitude of cognitive impairment in COVID-19 survivors was equivalent to the age-related cognitive decline expected during the 20year period between the ages of 50 and 70 years.

The studys lead author Professor David Menon, head of the Division of Anaesthesia at the University of Cambridge, says: Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw the cognitive fingerprint of COVID-19 was distinct from all of these.

Dr. Betty Raman, a cardiologist at the University of Oxford, told Medical News Today, This prospective cohort study of 46 individuals recovering from severe COVID-19 and large normative reference population by Hampshire and colleagues has shown a clear association between severity of infection and degree of cognitive impairment.

This multidimensional characterization of cognition provides a nuanced understanding of distinct patterns of cognitive impairment during the convalescent phase of severe COVID-19. Future efforts are needed to understand how this pattern varies in the context of other post-infectious syndromes and critical illness.

The study found that these cognitive deficits persisted until 6-10 months after the onset of COVID-19, and there was only a gradual improvement, if any, in cognitive performance. The persistence of these cognitive deficits highlights the importance of understanding the mechanisms underlying these symptoms.

Scientists have proposed multiple mechanisms, such as direct infection of the brain by SARS-CoV-2 and disruption of blood supply to the brain, to explain the persistent cognitive symptoms in COVID-19 patients. Among these mechanisms, systemic or whole-body inflammation has emerged as the leading candidate responsible for persistent cognitive symptoms.

Dr. Roger McIntyre, a professor of Psychiatry and Pharmacology at the University of Toronto, told MNT, Inflammatory activation appears to be mediating these findings, highlighting the hazards of lengthy immune activation. The next steps are to unravel biological mechanisms more fully and identify prevention and treatment strategies.

Discussing major questions that need to be addressed, Dr. Paul Harrison, a professor of psychiatry at the University of Oxford, said:

This study shows that these deficits can be substantial and persist more than 6 months after the acute illness. The results are convincing and important and raise further questions. For example, what happens following a less severe infection? How long do the deficits last? What causes them and, critically, how can they be treated or prevented?

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Severe COVID-19 may cause cognitive deficits equivalent to 20 years of aging - Medical News Today

Spinal Cord Stem Cells Comments Off on Severe COVID-19 may cause cognitive deficits equivalent to 20 years of aging – Medical News Today | May 13th, 2022

Osteoarthritis (OA) is the most common type of arthritis[1], and it is characterized by a progressive loss of articular cartilage, subchondral bone edema, sclerosis, synovitis, and marginal osteophyte formation. Pain, stiffness, and a restriction in joint movement are the most common symptoms whose severity varies. However, the condition gradually worsens over time and often results in significant functional impairment and reduced quality of life[2,3]. It was anticipated to become the fourth leading cause of disability by 2020[1,4,5], posing a significant socioeconomic burden impacting developed countries' gross domestic product[1,6]. Knee osteoarthritis (KOA) accounts for 85 percent of the global burden of OA and affects 19% of adults over 45-year-old and 37% of people over 60. KOA produces significant pain and physical impairment, lowering the quality of life and ranking as the eleventh leading cause of global disability. The average annual total expense per KOA patient is over US$15 000, resulting in total healthcare expenditure of nearly US$34 billion. Given population aging and the rise in obesity, KOA healthcare expenses are expected to quadruple by 2040[7]. It is necessary to develop sufficient medicines capable of slowing the progression of the disease and, as a result, preventing the loss of articular function and joint replacement. To provide more effective therapies, current conservative choices such as exercise and physiotherapy and weight loss with analgesics and naturally occurring substances should be integrated[1,8]. Developing effective conservative methods would be especially important for treating young people with early OA because their more active and physically demanding lifestyle negatively correlates with prosthetic implant survival[1,9].

The main treatment in the clinic is non-steroidal anti-inflammatory drugs (NSAIDs), which are recommended for all patients except those having surgical treatment in the American Academy of Orthopaedic Surgeons (AAOS) clinical practice recommendations for KOA treatment[10-12]. However, long-term usage of these treatments will cause major adverse reactions in patients, such as gastrointestinal ulcers, digestive system hemorrhage, and cardiovascular and cerebrovascular side effects, regardless of the toxicity of the drugs themselves[10,13]. Intra-articular injections of HA, platelet-rich plasma (PRP), or corticosteroids (CC) are also clinical possibilities, but their efficacy and the prevalence of side effects are still debated[10,14,15].

MSCs, be a possible treatment option for KOA[16-20]. MSCs, also called MPCs, secrete various cytokines that modulate an anti-inflammatory milieu in the OA joint, giving them immunomodulatory characteristics[18,21]. They may also have a unique ability to induce the growth of new cartilage-like cells in vitro[17,18,22], as improvements in cartilage morphology have been found in some situations[23-26]. These characteristics make them a suitable candidate for use in knee cartilage repair[27-32]. For OA treatment, orthobiologics injections containing MSCs as effector cells have recently been used. Because of their accessibility, bone marrow (BM) and adipose tissue (AD) have traditionally been the most used autologous tissue sources for orthopedic usage. In several studies, the use of autologous orthobiologics treatments in the treatment of OA is safe, with an extensive multicenter prospective analysis revealing no higher risk of neoplasia[33,34].

MSCs treatment looks to be safe based on published clinical study results. There were no significant side effects other than transitory fever in a comprehensive systematic review and meta-analysis of trials involving intravascular delivery of autologous or allogeneic expanded MSCs treatments (totaling over 1000 participants)[35,36]. A systematic evaluation of clinical trials involving intra-articular autologous expanded MSCs therapy that included 844 procedures. They had a mean follow-up of 21 months and found no link between infection, cancer, or death[35,37].

As a result, we undertook this study to examine all current high-quality information on the therapeutic efficacy and safety of MSCs in the treatment of KOA qualitatively and quantitatively. This is crucial, and the study's findings will give evidence and recommendations for the promotion and deployment of MSCs therapy in clinical practice.

We developed and implemented the study according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) system[38], the review's preferred reporting items.

Database

On December 30, 2021, we began our research using online libraries as a database. For our data gathering, we used PubMed, the Cochrane Library, and PMC.

Search Strategy

We included studies related to KOA, MSCs, and intra-articular injection. Our keywords and medical subject heading (MeSH) search strategies included knee, osteoarthritis, mesenchymal stem cells, intra-articular, and injection. The main MeSH terms used were: ("injections, intra articular"[MeSH Terms] OR ("injections"[All Fields] AND "intra articular"[All Fields]) OR "intra-articular injections"[All Fields] OR ("intra"[All Fields] AND "articular"[All Fields] AND "injection"[All Fields]) OR "intra articular injection"[All Fields]) AND ("mesenchymal stem cells"[MeSH Terms] OR ("mesenchymal"[All Fields] AND "stem"[All Fields] AND "cells"[All Fields]) OR "mesenchymal stem cells"[All Fields]) AND ("osteoarthritis, knee"[MeSH Terms] OR ("osteoarthritis"[All Fields] AND "knee"[All Fields]) OR "knee osteoarthritis"[All Fields] OR ("knee"[All Fields] AND "osteoarthritis"[All Fields])) and Knee Osteoarthritis, Mesenchymal Stem Cells, Intra-articular Injections. MeSH terms carried out a further supplementary search with free words. In addition, to prevent eliminating papers that satisfied the inclusion criteria, we searched retrieved studies that were cited.

Inclusion Criteria

We included RCTs and clinical trial studies conducted between 2017-and 2021, with complete free texts in the English language from all countries. Also, men and women aged 18 years or older with osteoarthritis in their knees and the severity of their osteoarthritis are shown in KL grade.

Exclusion Criteria

We excluded studies before the last five years, not in English, that included animals, HA, PRP, arthroscopy, ultrasound waves, and combination treatment in the intervention, other than knee joints like shoulder and hip.

Quality Assessment Tools

Two authors, S.S and S.V, independently assessed the study's overall quality and risk of bias by using the Cochrane Collaboration risk-of-bias tool for the RCTs and Newcastle Ottawa Scale (NOS) for the clinical trials. The Cochrane Collaboration risk-of-bias tool included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Each included RCT was rated as having a low, unclear, or high risk of bias based on these factors. The following are the contents for the NOS, including selection, comparability, and outcome. According to these items, each included clinical trial was scored as good, fair, and poor quality.

Data Extraction

Two writers, S.S and S.V, worked independently to extract data using a standardized manner. Disagreements that arose during the procedure were resolved through debate between the two writers or contact with a third author, just as they were with the inclusion of literature into the study. The following were the contents of the data extraction form: the first author's name, the year of publication, the sample size, basic patient information (age, male-to-female ratio, body mass index (BMI)), osteoarthritis grading KL grade, donor source (autogenous/allogeneic), cell processing, culture, and harvesting, number of cells, immunophenotype, intervention, and control situation, follow-up, and outcome clinical effectiveness and safety were among the outcomes.

Literature Search

Using the literature search, we discovered 78 relevant papers. After eliminating duplicates and screening titles and abstracts, 50 articles were excluded. The remaining 18 articles were subjected to a full-text review, with eight being excluded, as shown in figure1.

Characteristics of the Included Studies

A total of six RCTs (577 participants)[2,7,17,18,32,35], including one study which had a pilot study, commenced in November and completed in June 2021, where recruitment commenced in January and August 2021 and will be finished by December 2024[7]. Four clinical trial studies, including three prospective[16,23,32], and one retrospective[33]clinical trial, were included in this systematic review. Publication intervals for all 10 were from 2017 to 2021[7]. All studies used autologous MSCs except two studies[2,7], which used allogeneic MSCs. Five studies[2,17,18,35,39], used AD-MSCs two studies[23,32], used BM-MSCs, one study[16], used BMA, one study[33], used both concentrations BMAC and MFATand one study[7], used multipotent MSCs. A placebo was utilized as a control group[2,39]. For one study, NS was used as the control group[7]; for one trial, HA was used as the control group[17], In one study's control group, cautious management was adopted[35], and five of the investigations[16,18,23,32,33], were uncontrolled. Furthermore, four trials[2,16,17,35]were monitored for a year, three trials[7,23,32]were monitored for 24 months, and two trials[33,39]were followed for six months after they were completed, and one study[18], had a 48-weeks follow-up period. Table1illustrates the features of the 10 articles that were featured.

Risk of Bias Assessment

Figure2shows the results of the risk of bias evaluation for six studies[2,7,17,18,35,39], while table2shows the results of the NOS for four studies[16,23,32,33]. Lee et al.[39], although relevant images were drawn, we could not retrieve the original data and conduct the combined statistics; hence this study was classified as having a high risk of reporting bias. Freitag et al. and Kuah et al. incomplete data on overall WOMAC scores and subscales (pain, stiffness, and function) were also given, and one or more of these characteristics may have been missing. As a result, attrition bias was found to be considered a risk in these two investigations[2,35]. Freitag et al. performed BM or subcutaneous tissue extraction only in the intervention group. Even though moral restraint precluded the same measures from being used in the control group, this study was classified as having a high risk of detection and performance bias[35].

Outcomes

Knee Injury and Osteoarthritis Outcome Score (KOOS): A total of seven studies[7,16,23,32,33,35,39]reported KOOS[40]at baseline and final follow-up in the intervention and the control groups, including 650 patients. Three studies[7,23,32] were followed up for 24 months, two studies[16,35]were followed up for 12 months, and two studies[33,39]were followed up for six months. Normalized KOOS was used to measure positive changes in all five primary areas, and all were significantly better at six, 12, and 24-months post first injection[32]. Significant improvements in Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scores were observed over time (F (4,12) =12.29, p<0.001) in a cohort. Following the procedure, clinical significance was accomplished at three, six, and 12-months following the procedure[16]. As evaluated by normalized KOOS, table3demonstrates the favorable changes in all five essential categories. All were much improved at six, 12, and 24 months after the first treatment[32]. Using all sample time points, the Sport Score and quality of life (QOL) score were nominally linked with an unadjusted p-value of 0.031 and 0.046, respectively[23].

Magnetic Resonance Imaging (MRI) Evaluation

A total of eight studies reported MRI evaluation at baseline and follow-up in the groups, including 659 patients[2,7,17,18,23,32,33,39]. Three studies[7,23,32]were followed for a total of 24 months, for 12 months, two studies[2,17]were followed up on, and two studies[33,39]were followed up for six months after they were completed, and one study[18], had a 48-weeks follow-up period. The transformation of the central medial femorotibial compartment (cMFTC) cartilage thickness[41]for a 24-month was 0.32 mm (SD=0.40) for those who have narrowed medial tibiofemoral joint and maintained knee pain at baseline in comparison to the control neither of which radiographic nor pain development (0.12mm, SD=0.28)[7,42]. 67 percent of patients had progressed cartilage degeneration within the control group, with another 56 percent having extended osteophyte formation. Only 30% of individuals saw additional cartilage loss in the one-injection group, whereas 50% experienced osteophyte development advancement at 12 months. In the two-injection group, 89 percent of participants had cartilage improvement or no progression in cartilage loss, indicating that OA had stabilized, as seen by 89 percent of subjects having no progression in osteophyte formation[35]. The size of the cartilage defect in the MSCs group did not change substantially on MRI at six months (p =.5803), but the size of the cartilage defect in the control group grew significantly (p =.0049). Furthermore, the change in cartilage defect following the injection was significantly different between the two groups (p =.0051)[39]. Using the WORMS technique, the low-dose group had a mean change from baseline of -0.36 and -0.86 in both the left and right knees at week 48. Furthermore, the mean changes in total cartilage volume, knee femur end cartilage volume and knee patellar cartilage volume in the low-dose group were 54.58, 38.63, and 39.69 mm, respectively. The knee tibial end cartilage volume and knee cartilage volume in the medium-dose group improved by 243.32 and 34.44 mm, respectively. Increases of -0.42 and 122.92 mm in the left knee WORMS and knee femur end cartilage volume were reported in the high-dose group[18].

Two bilateral intra-articular knee injections, three weeks apart (18-20 days), were used in this preclinical study with AlloJoin. Because the high prevalence of bilateral KOA in the treatment population was investigated[18,43,44]. MRI showed no significant change in cartilage thickness after six months. As indicated in Table4, there was a considerable improvement in knee cartilage thickness in the femoral and tibia plates after 12 months[32]. Time 2 (T2) scores in the patella region increased by a negligible amount (p =.055 for a two-sided test, nonadjusted). T2 changes (from baseline to 12 months) did not differ across the one, 10, or 50 million BM-MSCs cohorts[23]. The 50 million BM-MSCs doses (effect estimate [B] = 1.828, p =.002) maintained synovitis at lower levels than the one million BM-MSCs dose, according to statistical analysis of the effects of dose adjusted for both time and baseline levels of synovitis[23]. We found a decrease in pro-inflammatory monocytes/macrophages in synovial fluid three months after MSCs infusion, suggesting a potential mechanism of action. We do not see statistical significance relative to baseline levels (p =.062) because of the small number of patients who presented synovial fluid at baseline and three months after MSC infusion (n = 5). However, this downregulation suggests a potential mechanism of action of MSCs in the arthritic joint[23].

Visual Analogue Scale (VAS)

A total of five studies[2,17,18,33,39]reported VAS evaluation at baseline and follow-up in the groups, including 194 patients. Two studies[2,17]were followed up for 12 months, two studies[33,39]were followed up for six months, and one study[18]was followed up for 48 weeks. VAS32[7], (P < .00001)[10], (p 0.005) in Progenza (PRG) combined group[2]. In the MSCs group exclusively, the VAS for knee discomfort dropped dramatically from 6.8 0.6 to 3.4 1.5 (p.001)[39]. Our VAS data confirmed clinical improvement with these cell injections, as seen by the study's reported VAS minimal clinical improvement differences (MCID) score of 30.0 mm[18,45,46].

Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC)

A total of six studies[2,17,18,23,35,39]reported WOMAC[47], evaluation at baseline, and follow-up in the groups, including 160 patients. Three studies[2,17,35]were tracked for 12 a year, one trial[23]was monitored for 24 months, one study[18]had a 48-weeks follow-up period, and for six months, one trial[39]was followed. (All P values were less than .05)[10]. Also, compared to the HA group, significantly more individuals had a 50% improvement in WOMAC, and after 12 months, the Re-Join group had a 70% improvement rate, indicating that more patients were improving[17].

At six months after injection, a single injection of AD-MSCs resulted in a 55 percent reduction in the WOMAC total score, a 59 percent reduction in the WOMAC pain score, a 54 percent reduction in the WOMAC stiffness score, and a 54 percent reduction in the WOMAC physical function score[39]. According to a study in previous research[24,48-50], clinical outcomes improved six months following MSCs injection. The findings of this investigation support this. Furthermore, similar to earlier research[49,50], even six months following injection, the clinical outcomes were still good. This finding implies that with a single intra-articular MSCs injection, symptom alleviation can be sustained for up to six months[39]. Improvements in short form 36 (SF-36), -23.71 in WOMAC total, -17.14 in WOMAC-function, -2.29 in WOMAC stiffness, and -4.29 in WOMAC-pain were seen in the low-dose cohort. Improvements in left knee VAS were -2.25, right knee VAS was -2.13, WOMAC-total was -16.50, WOMAC-function was -11.88, WOMAC-stiffness was -1.71, and WOMAC-pain was -3.25 in the medium-dose cohort. The high-dose cohort observed statistically significant improvements in the left knee VAS of -1.36 and the right knee VAS of -2.07[18]. The MCID averages for the WOMAC with KOA have been published[51]. The WOMAC functional score ranges between 9.1 to 19.9 mm, indicating that the WOMAC scores in this trial indicated considerable clinical improvement for the overall WOMAC functional (17.1) for both the left and right knees after 48 weeks for two of the doses[18,52-55].

Adverse Events (AEs)

A total of four studies[7,16,17,32]reported AEs evaluation at baseline and follow-up in the groups, including 550 patients. Two studies[7,32]were followed up for 24 months, and the others[16,17]were followed up for 12 months. Patient satisfaction was high (range: 8.12.1-8.81.9). All the patients said they would recommend the treatment to a friend, and 85 percent said they would do it again[16]. In the MSCs group, 10 (83%) patients experienced AEs, compared to seven (58%) individuals in the control group. No significant AEs or grade 4 or 5 AEs on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale. All the grade 3 AEs on the NCI-CTCAE scale were arthralgia, which completely disappeared within three days[39,56]. In the low-, middle-and high-dose groups, the incidence of AEs was 71.42 percent (5/7), 87.50 percent (7/8), and 100 percent (7/7), correspondingly[18].

We evaluated the clinical efficacy and safety of intra-articular injection of MSCs in this study by thoroughly analyzing six RCTs and four clinical trials. The study's first strength is its comprehensiveness, a compilation of all current high-quality studies. Second, we assessed the included studies' cell adherence, cell immunophenotype, and cell differentiation ability using the MSC criteria established by the Mesenchymal Stem Cell Committee of the International Society for Cell Therapy (ISCT), and discovered that half of them meet the minimum requirements[16,18,23,35,39], as shown in table1. Third, it contains tight inclusion and exclusion rules. Concurrent therapy studies, such as HA and PRP were omitted. The addition of newly incorporated research of AT and BM sources, we believe, is what has led to the divergent results. This is one of the reasons we are so adamant about completing this research. Compared to the control group, the MSCs group showed a considerable increase in cartilage volume.

The selection of the appropriate donor source and the optimal dose has become an essential issue due to the extensive research into MSCstherapy. BM, AT, placenta, and umbilical cord are among the most popular donor sources for MSCs in clinical research. Initially, people preferred to cultivate and expand BM-MSCs. Later research discovered that AT was more accessible than BM, had a simpler isolation technique, a larger yield, and the same chondrogenic capacity[10,57,58].

A reduction in pain is connected to the ability of cells to release bioactive chemicals. These elements are hypothesized to change the inflammatory milieu in the joint from pro-inflammatory to anti-inflammatory. PRG includes a high concentration of these bioactive substances in the cell culture supernatant, unlike other cell therapies. PRG may decrease the progression of OA based on the favorable cartilage outcomes from preclinical and clinical investigations. Many studies have found that beneficial effects are primarily apparent in the lateral tibial region. Although OA affects the entire joint, it has been hypothesized that the medial tibiofemoral region is more severely damaged than the lateral tibiofemoral region. As a result, because the medial tibiofemoral region is later, there may be fewer opportunities to demonstrate progress[2].

MPCs tagged with fluorescent dye lasted locally in the joint for up to 10 weeks in preclinical rat studies before becoming undetectable[18,59]. Furthermore, the serious adverse events (SAEs) contradict all preclinical animal investigations that revealed no evidence of systemic exposure[18,59-61]. In addition, earlier research has shown that Re-Join is beneficial in rabbit and sheep models of OA[17,60,61]. The repair of osteoarthritis in rabbits and goats appears to be mediated by paracrine effects involving the stimulation of endogenous repair systems[26,32]. In a systematic evaluation of MSCs therapies, Lalu et al. found no significant side effects[23,62,63]. Following the aspiration of BM, there were no systemic side effects observed, and there were no issues that were noted[23]. Therefore, no individuals dropped out of the study[2].

Our findings show that there are statistically significant improvements in pain and function[2,7,10,16-18,33,35]. The average percentage of patients who have passed the Patient-Acceptable Symptom State (PASS)[64]the threshold was 35% in the placebo cohort(ranging from 33.1 to 35.5) and 48% in the intervention cohorts (varying between 42.2% to 56.1%)[7,65,66]. There were also decreases in present, typical, best, and worst numerical rating scale (NRS) pain[67], scores statistically significant over time (F(4,12)=14.5, p<0.001; F(4,12)=17.5, p<0.001; F(4,12)=2.9, p=0.003; and F(4,12)=35.5, p<0.001, respectively)[16]. Also, NRS pain in both the single and two injection protocol treatment groups, when compared to baseline, within-group improvement was statistically significant (0.05) at all time intervals[35]. Therefore, we found that all statistical tests for pain and functional outcome measures (n = 21) had a mean power of 0.877 15 SD[35]. The NPRS improved by 69 percent from baseline to the last follow-up at 12 months in both therapy groups. In comparison, arthroscopic debridement resulted in a 14 percent improvement in pain scores after 12 months, while a prescribed exercise regimen resulted in a 12 percent improvement in pain scores[35,68,69]. The range of motion in the MSCs group improved considerably from 127.9 10.3 to 134.6 12.5 at six months after injection (p =.0299)[39]. When these established MCID values were applied at 48 weeks, there was a reduction in pain and an improvement in knee function; however, due to the small number of participants included in this pilot investigation, these findings should be regarded with caution[18].

In addition, they discovered a link between the number of cells injected and pain relief[33]. Furthermore, two RCTs were recently reported, revealing significant improvements in pain and function in KOA patients after injection of autologous AD-MSCs versus controls[33]. MSCs generated from autologous BM showed a significant increase in clinical ratings[33,39]. Because the researchers differ in study design, cell type, supplementary therapy, and rehabilitation methods, it is difficult to determine the true differences in intra-articular injections of BM-MSCs and AD-MSCs[39].

Data reveal that one or more outcomes, such as KOOS pain, have improved statistically significantly[23,32,35], symptoms, SF-36[18], VAS[2,10,16,18,33,39], and QOL scores[17,23,33], as well as WOMAC stiffness[2,10,16-18,23,33,35,39]. NPRS improved[16,35], from baseline to final follow-up at 12 months, by a percentage of 69 percent previous clinical trials have shown that intra-articular MSCs treatment can slow the course of OA[35]. All symptoms decreased dramatically, resulting in a considerable improvement in the quality of life of these grade 2 to 4 KOA patients. There is also evidence of safety. However, more research is required. Another concern is that most research focuses on short-term safety rather than long-term results[32]. Starting three months after the procedure, KOOS-JR scores improved dramatically, with clinically meaningful improvements lasting 12 months[16]. Within 48 weeks of follow-up, MCID scores for SF-36 are approximately 10%, which this study's data has surpassed[18,53,70,71]. Both groups improved significantly in Emory Quality of Life (EQOL), VAS, and all KOOS indicators pre-and post-procedure (p < .001)[33]. During follow-up, the two treatment groups' EQOL ratings altered in similar ways (similar temporal patterns across time) (p =0.98, test for interaction between time on study and treatment group)[33].

We report putative chondroprotective benefits and decreased synovial inflammation, with the 50 million cell dosage potentially being more beneficial. However, when compared to the 50 million and/or 10 million BM-MSC dosages, serum carboxy-terminus of the three-quarter peptide from cleavage of C I and C II (C1, C2), urine type II collagen cleavage neoepitope (C2C), and C-telopeptide of type II collagen (CTX-II) all increased significantly, suggesting a chondroprotective MSCs dose effect, as previously described[23]. Furthermore, exploratory MRI analyses of average cartilage volumes and average WORMS from baseline at week 48 revealed no change in the medium-dose (2*107 cells) and high-dose (5*107 cells) groups but an improvement in the low-dose AlloJoin (1*107 cells) group[18]. Over radiography x-rays, MRI assessments offered a more accurate picture of articular cartilage deterioration and change in location of the menisci[18,72]. Because MOAKS[73]is a semi-quantitative metric, the MRI analysis is limited[18]. Furthermore, MOAKs analysis demonstrating effective stabilization despite continuous bone marrow lesions (BMLs)contrasts with previous research that has found a link between BMLs and OA progression[35].

Because Orozco et al. showed a consistent improvement in cartilage quality during a two-year follow-up period from the baseline, we expect cartilage improvement in our series over a longer follow-up time[39,48]. Our research also saw increased cartilage volume and quality[2,17,18,23,32,39]. Furthermore, an MRI examination at 48 weeks revealed no signs of ectopic bone development[18]. Intra-articular injections of Re-Join were found to enhance cartilage volume, with a significant rise 12 months after injection, suggesting that this could be a viable therapeutic intervention and cartilage regeneration for OA patients[17].

We believe that the subsequent trials should be greater[23]. The following trials should, in our opinion, be larger[18]and also look at the MSCs dose and the MSCs source. The safety of allogeneic MSCs for KOA must be established[23,32,39]. The usage of allogenic MSCs can be standardized, the dose can be more precisely regulated, and cell variability may be minimized. We should also examine the efficacy of BM and AD-derived orthobiologics treatments to develop a reliable judgment on which is the better choice for treating KOA[33]. MSCs, we feel, has the potential to be a definitive treatment for KOA[32]. It is also critical to distinguish the findings of this study from those of previous studies that used more various cell-based products, such as stromal vascular fraction[35].

This research has several limitations. The results should be treated with care first and foremost. We did our utmost to avoid simultaneous surgical treatment affecting efficacy. Second, all the studies we looked at used intra-articular injections. MSCs implantation by open or arthroscopic surgery has been proven to be more conducive to cartilage repair in several studies. While MSCs transplantation on a scaffold may help rebuild the anterior cruciate ligament and meniscus[10]. Third, four of our studies[16,23,32,33], were not RCTs. Fourth, we included three studies[23,33,39]that included KL grade 4 KOA patients. We do not know if the disease can be slowed or even reversed at this point in the disease's progression, especially using autologous-derived MSCs. Furthermore, as the human body ages, MSCs' ability to self-renew and differentiate decreases; particularly, the potential of MSCs in individuals with OA is lower than that of healthy persons[10,17,23,33,35].

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Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review - Cureus

Bone Marrow Stem Cells Comments Off on Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review – Cureus | May 13th, 2022

You should read the following discussion and analysis of our financial conditionand results of operations together with the condensed consolidated financialstatements and related notes included in Part I, Item 1 of this Quarterly Reporton Form 10-Q (this "Quarterly Report") and with the audited financial statementsand the related notes included in our Annual Report on Form 10-K for the fiscalyear ended December 31, 2021 filed with the Securities and Exchange Commissionon March 18, 2022. Certain of the information contained in this discussion andanalysis or set forth elsewhere in this Quarterly Report, including informationwith respect to plans and strategy for our business, includesforward-looking statements that involve risks and uncertainties. As a result ofmany factors, including those factors set forth in the section entitled "RiskFactors", in Part II, Item 1A of this Quarterly Report, our actual results coulddiffer materially from the results described in or implied by theforward-looking statements contained in the following discussion and analysis.You should carefully read the section entitled "Risk Factors" to gain anunderstanding of the important factors that could cause actual results to differmaterially from our forward-looking statements. Please also see the section ofthis Quarterly Report entitled "Cautionary Note RegardingForward-Looking Statements." The events and circumstances reflected in ourforward-looking statements may not be achieved or may not occur, and actualresults could differ materially from those described in or implied by theforward-looking statements contained in the following discussion and analysis.As a result of these risks, you should not place undue reliance on theseforward-looking statements. We assume no obligation to revise or update anyforward-looking statements for any reason, except as required by law.OverviewWe are a clinical-stage biotechnology company dedicated to enabling curesthrough hematopoietic stem cell therapy. We are focused on the development andcommercialization of safer and more effective conditioning agents and mRNA-basedstem cell engineering to allow for expanded use of stem cell transplantation andex vivo gene therapy, a technique in which genetic manipulation of cells isperformed outside of the body prior to transplantation. We are also developingnovel therapeutics directed at diseased hematopoietic stem cells.Our drug development pipeline includes multiple product candidates designed toimprove hematopoietic stem cell therapy. Our lead product candidate, JSP191, isin clinical development as a novel conditioning antibody that clearshematopoietic stem cells from bone marrow in patients prior to undergoingallogeneic stem cell therapy or stem cell gene therapy. We plan to initiate aregistrational clinical study in acute myeloid leukemia ("AML") patientsundergoing stem cell transplantation by the end of the first quarter of 2023.Based on the single agent depletion observed in our Phase 1 study ofmyelodysplastic syndrome ("MDS") patients undergoing stem cell transplant, weare also initiating a pilot study of JSP191 as a therapeutic in lower-risk MDS,which we expect to commence in the second half of this year. Beyond JSP191, weare developing stem cell grafts transiently reprogrammed using mRNA that have acompetitive advantage over endogenous hematopoietic stem cells ("HSCs"),enabling higher levels of engraftment designed to remove the need for highlytoxic conditioning of the patient and lower the risk of other seriouscomplications that limit current stem cell transplants. We plan to continue toexpand our pipeline to include other novel stem cell therapies based on immunemodulation, graft engineering and cell or gene therapies. Our goal is to expandthe use of curative stem cell transplant and gene therapies for all patients,including children and the elderly.Stem cell transplantation is among the most widely practiced forms of cellulartherapy and has the potential to cure a wide variety of diseases, includingcancers, genetic disorders, and autoimmune diseases. Yet currently, patientsmust receive highly toxic and potentially life-threatening conditioning agentsto prepare their bone marrow for transplantation with either donor stem cells ortheir own gene-edited stem cells. Younger, fitter patients capable of survivingthese toxic side effects are typically given myeloablative, or high-intensity,conditioning whereas older or less fit patients are typically given reducedintensity, but still toxic, conditioning which leads to less effectivetransplants. These toxicities include a range of acute and chronic effects tothe gastrointestinal tract, kidneys, liver, lung, endocrine, and neurologictissues. Depending upon the conditioning regimen, fitness of the patient, andcompatibility between the donor and recipient, the risk of transplant-relatedmortality ranges from 10% to more than 50% in older patients. Less toxic ways tocondition patients have been developed to enable transplant for older patientsor those with major comorbidities, but these regimens risk less potent diseaseelimination and higher rates of disease relapse. Even though stem cell therapycan be one of the most powerful forms of disease cure, these limitations ofnon-targeted conditioning regimens have seen little innovation over the pastdecade. 20Our lead product candidate, JSP191, is a monoclonal antibody designed to blockthe specific signal on stem cells required for survival. It is currently indevelopment as a highly targeted conditioning agent prior to stem cell therapyas well as a therapeutics in lower-risk MDS patients, which we expect tocommence in the second half of 2022. We are also sponsoring two clinical studiesof JSP191 as a conditioning agent prior to stem cell transplant. The firstclinical study is an open label Phase 1/2 trial in two cohorts of severecombined immunodeficiency ("SCID") patients: patients with a history of a priorallogeneic transplant for SCID but with poor graft outcomes and newly diagnosedSCID patients. The primary endpoint in this study is to evaluate the safety andtolerability of JSP191. The secondary goal of this study is to evaluate theefficacy of JSP191 as a conditioning agent in conjunction with a stem celltransplant. Based on preliminary results from our ongoing Phase 1/2 clinicaltrial, we believe JSP191 has demonstrated the ability as a single agent toenable engraftment of donor HSCs as determined by donor chimerism, or thepercentage of bone marrow cells in the patient that are of donor origin aftertransplant. Engraftment was observed in seven out of ten T-B-NK+ SCID patientswith prior allogeneic transplant, as evidenced by CD15+ donor chimerism of morethan 5% averaged from 12-24 weeks post-transplant. Increased nave donor T cellproduction was observed in the majority of T-B-NK+ subjects, as well as clinicalimprovement. No JSP191 treatment-related serious adverse events ("SAEs") havebeen reported to date and pharmacokinetics have been consistent with earlierstudies in healthy volunteers. We expect to complete enrollment in this Phase1/2 clinical trial by mid-2023.

The FDA has granted rare pediatric disease designation to JSP191 as aconditioning treatment for patients with SCID. In addition, the FDA grantedorphan drug designation to JSP191 for conditioning treatment prior tohematopoietic stem cell transplantation.

We expect our expenses will increase substantially in connection with ourongoing and planned activities, as we:

? advance product candidates through preclinical studies and clinical trials;

? procure the manufacture of supplies for our preclinical studies and clinical

? attract, hire and retain additional personnel;

? operate as a public company;

? implement operational, financial and management systems;

? pursue regulatory approval for any product candidates that successfully

? establish a sales, marketing, and distribution infrastructure to commercialize

any product candidate for which we may obtain marketing approval and related

commercial manufacturing build-out; and

? obtain, maintain, expand, and protect our portfolio of intellectual property

Business Impact of the COVID-19 Pandemic

Stanford License Agreement

Other collaboration and clinical trial agreements

Collaboration with Stanford University

Components of Results of Operations

External research and development costs include:

? costs incurred under agreements with third-party CROs, CMOs and other third

parties that conduct preclinical and clinical activities on our behalf and

manufacture our product candidates;

? costs associated with acquiring technology and intellectual property licenses

that have no alternative future uses;

? consulting fees associated with our research and development activities; and

? other costs associated with our research and development programs, including

Internal research and development costs include:

? employee-related costs, including salaries, benefits and

stock-based compensation expense for our research and development personnel;

? other expenses and allocated overheads incurred in connection with our research

Our future research and development costs may vary significantly based onfactors, such as:

? the scope, rate of progress, expense and results of our discovery and

preclinical development activities;

? the costs and timing of our chemistry, manufacturing and controls activities,

including fulfilling cGMP-related standards and compliance, and identifying and

? per patient clinical trial costs;

? the number of trials required for approval;

? the number of sites included in our clinical trials;

? the countries in which the trials are conducted;

? delays in adding a sufficient number of trial sites and recruiting suitable

patients to participate in our clinical trials;

? the number of patients that participate in the trials;

? the number of doses that patients receive;

? patient drop-out or discontinuation rates;

? the duration of patient participation in the trials and follow up;

? the cost and timing of manufacturing our product candidates;

? the phase of development of our product candidates;

? the efficacy and safety profile of our product candidates;

? the timing, receipt, and terms of any approvals from applicable regulatory

authorities, including the FDA and non-U.S. regulators;

? maintaining a continued acceptable safety profile of our product candidates

following approval, if any, of our product candidates;

? changes in the standard of care on which a clinical development plan was based,

which may require new or additional trials;

? the extent to which we establish additional strategic collaborations or other

? the impact of any business interruptions to our operations or to those of the

Other Income (Expense), Net

Three Months Ended March 31, 2022 and 2021

The following table summarizes our results of operations for the three monthsended March 31, 2022 and 2021 (in thousands):

Research and Development Expenses

The following table summarizes our research and development expenses for thethree months ended March 31, 2022 and 2021 (in thousands):

Our external costs by program for the three months ended March 31, 2022 and 2021were as follows (in thousands):

General and Administrative Expenses

Liquidity and Capital Resources

Future Funding Requirements - Going Concern

Contractual Obligations and Commitments

We have contractual obligations and commitments as described in Note 9,Commitments and Contingencies, within our condensed consolidated financialstatements included in Part I, Item 1 of this Quarterly Report.

Our future financing requirements will depend on many factors, including:

? the timing, scope, progress, results and costs of research and development,

preclinical and non-clinical studies and clinical trials for our current and

? the number, scope and duration of clinical trials required for regulatory

approval of our current and future product candidates;

? the outcome, timing and costs of seeking and obtaining regulatory approvals

from the FDA and comparable foreign regulatory authorities for our product

candidates, including any requirement to conduct additional studies or generate

additional data beyond that which we currently expect would be required to

support a marketing application;

? the costs of manufacturing clinical and commercial supplies of our current and

future product candidates;

? the costs and timing of future commercialization activities, including product

manufacturing, marketing, sales and distribution, for any of our product

candidates for which we receive marketing approval;

? any product liability or other lawsuits related to our product candidates;

? the revenue, if any, received from commercial sales of any product candidates

for which we may receive marketing approval;

? our ability to establish a commercially viable pricing structure and obtain

approval for coverage and adequate reimbursement from third-party and

? the costs to establish, maintain, expand, enforce and defend the scope of our

intellectual property portfolio, including the amount and timing of any

payments we may be required to make, or that we may receive, in connection with

licensing, preparing, filing, prosecuting, defending and enforcing our patents

or other intellectual property rights;

? expenses incurred to attract, hire and retain skilled personnel;

? the costs of operating as a public company; and

? the impact of the COVID-19 pandemic, which may exacerbate the magnitude of the

10,752

Cash Flows Used in Operating Activities

Net cash used in operating activities was $14.2 million and $6.2 million for thethree months ended March 2022 and 2021, respectively.

Cash Flows Used in Investing Activities

Cash Flows from Financing Activities

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JASPER THERAPEUTICS, INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - Marketscreener.com

Bone Marrow Stem Cells Comments Off on JASPER THERAPEUTICS, INC. Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) – Marketscreener.com | May 13th, 2022

Aileron Therapeutics, Inc.

Taxanes, such as paclitaxel and docetaxel, cause severe and often permanent chemotherapy-induced hair loss (alopecia)

New non-clinical data demonstrate proof of principle that ALRN-6924 can temporarily arrest the cell cycle in human scalp hair follicles and their stem cells

ALRN-6924-induced cell cycle arrest protected hair follicles from paclitaxel-induced toxicity and irreversible stem cell damage

Ailerons precision medicine-based approach is designed to selectively protect normal, healthy cells from chemotherapy while ensuring chemotherapy cannot protect cancer cells

Ailerons ongoing non-small cell lung cancer (NSCLC) clinical trial and upcoming breast cancer clinical trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities and other side effects, including alopecia

BOSTON, May 10, 2022 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives, today announced a late-breaking oral presentation at the upcoming Society for Investigative Dermatology (SID) Annual Meeting, which will be held May 18 21, 2022 in Portland, Oregon. The presentation will highlight new non-clinical data developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues at the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery at the University of Miami Miller School of Medicine. This collaboration has generated promising ex vivo data demonstrating that ALRN-6924 protected human hair follicles and their stem cells from chemotherapy-induced acute and permanent damage. Details of the presentation are as follows:

Title:

ALRN-6924, a dual inhibitor of MDMX and MDM2, protects human scalp hair follicles and their epithelial stem cells from paclitaxel-induced toxicity (LB1018)

Presenter:

Jennifer Gherardini, Ph.D.; Paus Laboratory, University of Miami Miller School of Medicine

Date:

Thursday, May 19th

Time:

8:45 AM 11:15 AM PT

Session:

Late-Breaking Abstract Concurrent Session

Chemotherapy-induced toxicities range from severe and life-threatening to those that impact and diminish patients quality of life, sometimes long after chemotherapy has been completed. These toxicities occur because chemotherapy destroys normal, healthy cells while simultaneously destroying cancer cells, said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. Previously, we showed chemoprotection against severe bone marrow toxicities in small cell lung cancer patients receiving topotecan and demonstrated in healthy volunteers the mechanism of action cell cycle arrest underlying this chemoprotection benefit. We are excited to now present new data that may suggest ALRN-6924s ability to also protect against chemotherapy-induced hair loss, another devastating chemotherapy-induced side effect for millions of cancer patients.

Dr. Paus commented, These results got us quite excited as they directly follow in the footsteps of our prior work that showed arresting the cell cycle can have a strong protective effect against taxane-induced hair follicle damage. Until our research with ALRN-6924, we had not come across a cell cycle arrest-inducing drug that is in clinical testing for protection of normal cells without protecting cancer cells. Thus, ALRN-6924 invites a very promising and completely novel selective protection approach. In addition, we found that ALRN-6924 may exert some additional benefits that could reduce the risk of long-term damage of human hair follicle stem cells by taxanes.

Story continues

Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapys attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells. The companys vision is to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy.

About the Findings

Taxanes, such as paclitaxel and docetaxel, are known to cause severe and often permanent chemotherapy-induced alopecia. Over 90% of patients treated with this chemotherapy class experience alopecia, and approximately 10% (paclitaxel) to 25% (docetaxel) of patients experience permanent alopecia. Dr. Paus and his team previously demonstrated that paclitaxel damages human scalp hair follicles by inducing massive mitotic defects and apoptosis in hair matrix keratinocytes as well as bulge stem cell DNA damage, and that pharmacological induction of transient cell cycle arrest can protect hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron previously conducted in vitro studies showing that ALRN-6924 protected human fibroblasts in cell culture from multiple chemotherapies, but not p53-mutant breast cancer cells.

In the new non-clinical findings to be presented at the SID meeting, when organ-cultured anagen (i.e., active growth phase) scalp hair follicles from two human donors were pre-treated with ALRN-6924 or vehicle (i.e., placebo), followed by paclitaxel or vehicle, ALRN-6924 significantly increased the number of p21-positive hair matrix keratinocytes and bulge stem cells compared to vehicle or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a reduction in the number of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, as well as a reduction in apoptosis, pathological mitosis, and DNA damage. Aileron believes that these findings support clinical investigation of ALRN-6924 to prevent both acute and permanent chemotherapy-induced alopecia, in addition to its ongoing evaluation of ALRN-6924 to protect against chemotherapy-induced bone marrow and other toxicities.

About Ailerons Clinical Trials of ALRN-6924

Aileron is on track to initiate a Phase 1b randomized, controlled trial of ALRN-6924 in patients with p53-mutated ER+/HER2- neoadjuvant breast cancer in 2Q 2022. The planned breast cancer trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities, as well as other toxicities, including alopecia, in patients with p53-mutated ER+/HER2- breast cancer treated with a doxorubicin plus cyclophosphamide and docetaxel chemotherapy regimen.

The company is currently enrolling patients in a Phase 1b randomized, double-blind, placebo-controlled trial evaluating ALRN-6924s protection against chemotherapy-induced bone marrow and other toxicities in patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. While patients in this trial are monitored for alopecia, historically, only a small percentage of patients treated with carboplatin plus pemetrexed experience acute alopecia. Aileron is on track to report interim results on the first 20 patients enrolled in the NSCLC trial in June 2022 and topline results on 60 patients in 4Q 2022.

About Aileron Therapeutics

Aileron is a clinical stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.

Our vision is to bring chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.

Forward-Looking Statements

Statements in this press release about Ailerons future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective agent, including its ability to prevent both acute and permanent chemotherapy-induced alopecia, and the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether initial results of clinical trials will be indicative of final results of those trials or results obtained in future clinical trials, including trials in different indications; whether ALRN-6924 will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will be accepted by and warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive approval from regulatory agencies on a timely basis or at all or in which territories or indications ALRN-6924 may receive approval; whether, if ALRN-6924 obtains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on the timing of our clinical development, clinical supply and our operations; and other factors discussed in the Risk Factors section of Ailerons annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Investor Contact:Stern Investor RelationsAlexander Loboalex.lobo@sternir.com

Media Contact:Liz Melone617-256-6622

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Aileron Therapeutics Announces Late-Breaking Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their...

Bone Marrow Stem Cells Comments Off on Aileron Therapeutics Announces Late-Breaking Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their… | May 13th, 2022

SAN DIEGO, Calif., SUZHOU and SHANGHAI, China , May 12, 2022 /PRNewswire/ -- Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, today announced the details of three abstracts that it will present at the European Hematology Association 2022 Hybrid Congress (EHA2022 Congress), being held from June 9 June 12 in Vienna, Austria. The abstracts highlight the clinical data from ongoing investigator-initiated trials (IITs) of BCMA/CD19 dual-targeting FasTCAR candidate GC012F in two indications of B-cell non-hodgkin's lymphoma (B-NHL) and relapsed/refractory multiple myeloma (RRMM), and allogeneic TruUCAR candidate GC502 in B-cell acute lymphoblastic leukemia (B-ALL).

"We are very excited to share our data for both our FasTCAR candidate GC012F in two indications of RRMM and B-NHL, and allogeneic TruUCAR candidate GC502 in B-ALL at the EHA2022 Congress," said Dr. Martina Sersch, Chief Medical Officer of Gracell. "The new data, including the expanded indication of GC012F into B-NHL, demonstrates the potential of our platforms and provides further validation. The clinical data of BCMA/CD19 dual-targeting GC012F in the treatment of B-NHL shows promising early results, along with benefits of the next-day manufacturing enabled by the FasTCAR platform. The CD19/CD7 dual-directed CAR-T therapy GC502 is our second allogeneic candidate on our TruUCAR platform, demonstrating the potential wide applicability of the TruUCAR design."

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of B-NHL

GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19. It is developed using Gracell's proprietary FasTCAR platform which enables next-day manufacturing, and is currently being evaluated in IITs in China including in RRMM and B-NHL. GC012F is the first BCMA/CD19 dual-targeting CAR-T in human trials for B-NHL.

Gracell will present the early results of the first-in-human phase 1 IIT in China evaluating the safety and tolerability of GC012F in B-NHL patients. Three patients who had received a median of two prior lines of therapy were enrolled, all of which presented with bulky disease. As of the February 22, 2022 data cutoff date, the enrolled patients had received one single infusion of GC012F at three different doses of 3.7x104 cells/kg and 2-3x105 cells/kg.

All three patients had achieved a complete response (CR) confirmed by PET- CT at day 28 after GC012F infusion. At 3-month follow-up, both of the two assessable patients had ongoing response. No dose-limiting toxicities were observed and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. CRS presented as Grade 1 in two patients and Grade 3 in one patient (duration of two days) with no Grade 4 or 5 events.

Details of the presentation are as follows:

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of RRMM

Gracell will also present as an oral abstract presentation the updated results from the first-in-human IIT evaluating GC012F for the treatment of RRMM patients. This data is currently under embargo and will be published on the EHA2022 Hybrid Congress website on Thursday, May 26 concurrently with ASCO.

Details of the presentation are as follows:

CD19/CD7 Dual-directed Allogeneic TruUCAR-T GC502 for the Treatment of B-ALL

GC502 leverages the novel dual-directed CAR design of Gracell's proprietary TruUCAR platform, designed to generate high-quality allogeneic CAR-T cell therapies that can be administered "off-the-shelf" at lower cost and with faster patient's access. TruUCAR-enabled GC502 utilizes the dual-directed CAR design with one CAR targeting CD19 on malignant cells and a second CAR targeting CD7 to suppress host-versus-graft rejection. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells.

Between September 2021 and January 2022, four r/r B-ALL patients were enrolled and treated in an open-label, non-randomized, prospective IIT in China in two different dose levels and with two different formulations. Patients were heavily pretreated, and all had previously received either autologous or donor derived CD19 or CD19/CD22 targeted CAR-T therapy. As of the January 28, 2022 data cutoff date, all four patients had received a single dose of GC502, including one patient at dose level 1 (DL1) 1.0x107 cells/kg and three patients at dose level 2 (DL2) 1.5x107 cells/kg. Patients received a Flu/Cy based lymphodepletion regimen prior to treatment with GC502.

Three of four patients achieved minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi), and one patient achieved a partial response at month one and subsequently received allogeneic hematopoietic stem-cell transplantation (allo-HSCT) on day 39.

Cytokine release syndrome (CRS) presented as Grade 2 and Grade 3 with no Grade 4 or 5 events. No immune effector cell-associated neurotoxicity syndrome (ICANS) or acute graft-versus-host disease (aGvHD) were observed.

Details of the presentation are as follows:

For more information about the EHA2022 Hybrid Congress, visit http://www.ehaweb.org.

About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin's lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About B-NHL

Non-Hodgkin's lymphoma (NHL) is a group of blood cancers that developed from lymphocytes, most commonly derived from B cells (B-NHL). Globally, approximately 510,000 patients are diagnosed with NHL every year with about 80,470 patients expected to be diagnosed with NHL in the United States in 2022[1]. B-NHL accounts for approximately 85% of NHL diagnoses.

[1] Data source: American Cancer Society

About GC502

GC502 is a TruUCAR-enabled CD19/CD7 dual-directed, off-the-shelf allogeneic CAR-T product candidate that is being studied in an ongoing Phase 1 IIT in China for the treatment of B-cell malignancies. GC502 is manufactured using T cells from non-human leukocyte antigen (HLA) matched healthy donors. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells. Optimized for CD19/CD7 dual-CAR functionality and in vivo durability, GC502 has demonstrated robust anti-tumor effects with potential to suppress host versus graft (HvG) rejection in preclinical models.

About B-ALL

Acute lymphoblastic leukemia (ALL) is a type of blood cancer characterized by proliferation of immature lymphocytes in the bone marrow, which can involve either T lymphocytes (T-ALL), or B lymphocytes (B-ALL). Globally, approximately 64,000 patients are diagnosed with ALL every year with an estimated 6,660 new cases to be diagnosed in the United States in 2022[2]. B-ALL accounts for 75% of ALL diagnoses in adults.

[2] Data source: American Cancer Society

About FasTCAR

CAR-T cells manufactured on Gracell's proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.

About TruUCAR

TruUCAR is Gracell's proprietary technology platform and is designed to generate CAR-T cell therapies from high quality allogeneic T cells that can be administered "off-the-shelf" at lower cost and with improved accessibility of cell therapies for cancer patients. With differentiated design enabled by gene editing, TruUCAR is designed to control HvG as well as GvHD without the need for being co-administered with additional strong immunosuppressant after conventional lymphodepletion. The novel dual-CAR design allows tumor antigen-CAR moiety to target malignant cells, while the CD7 CAR moiety is designed to suppress rejection (HvG response) of allogeneic CAR-T cells by host T and NK cells (HvG).

About Gracell

Gracell Biotechnologies Inc.("Gracell") is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CARTMtechnology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost, and lack of effective CAR-T therapies for solid tumors. For more information on Gracell, please visit http://www.gracellbio.com.Follow @GracellBio on LinkedIn.

Cautionary Noted Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the expected trading commencement and closing date of the offering. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the section entitled "Risk Factors" in Gracell's most recent annual report on Form 20-F as well as discussions of potential risks, uncertainties, and other important factors in Gracell's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Gracell specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon the information on this page as current or accurate after its publication date.

Media contacts

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Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic...

Bone Marrow Stem Cells Comments Off on Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic… | May 13th, 2022

Dr. Sara Vasconcelos in the laboratory at Toronto General Hospital on May 11.Christopher Katsarov/The Globe and Mail

When Sara Vasconcelos talks about her work, it sounds as if shes in the restoration business. But instead of repairing damaged buildings, the researcher at Torontos University Health Network wants to fix damaged hearts by using stem cells to rebuild cardiovascular tissue.

Now, Dr. Vasconcelos is one step closer to achieving that goal with a $3-million grant from the Stem Cell Network, a Canadian research funding organization. Her effort is one of 32 projects across the country that rose to the top in a competition for in the largest outlay of federal funding for regenerative medicine in 20 years.

On Thursday, the Ottawa-based network announced a total of $19.5-million in awards, which together with matching funds from various partners, will translate into $42-million for research and clinical trials over the next three years. The funding will enable the work of more than 400 scientists, clinicians and trainees, the organization said.

Its a big step, said Dr. Vasconcelos, who said she will use her award to build on preliminary findings obtained using rats. She will next work with pig hearts, which offer a much closer analogue to the human organ.

While doing so, she also hopes to overcome a barrier that has stood in the path of those who are trying to repair hearts using cardiomyocytes heart tissue cells that are grown from embryonic stem cells. The problem is that the replacement cells wither away if they are not nourished and kept alive by blood vessels.

As part of her project Dr. Vasconcelos aims to use a technique in which small sections of microscopic blood vessels are harvested from human fat and implanted along with the heart cells.

The microvessels that are like Lego pieces, she said. You can put a whole bunch of them in with the stem cell-derived cardiomyocytes and they will connect to each other and connect to the host vessels that carry blood.

With her grant secured, Dr. Vasconcelos said she is assembling the team that will test the method on pig hearts later this year. Ultimately, her goal is to develop the technique into a therapy that can restore cardiac function in human patients following a heart attack, she said.

Among the other projects to win funding are some that are already heading for clinical studies. That includes a large study led by Guy Sauvageau, a hematologist at Maisonneuve-Rosemont Hospital in Montreal, that involves developing engineered blood stem cells to treat leukemia.

Working with a group of clinical sites in the U.S., Dr. Sauvageau and his team have already had success at treating patients with leukemia who relapse. The new project will involve introducing genetical engineered stem cells into people who are better able to withstand cancer treatment and facilitate recovery.

Between 10,000 and 20,000 patients a year would benefit from this kind of therapy, Dr. Sauvageau said.

In the future, he added, the study could open the door to teaching the body to continually produce and replenish its own cancer-killing immune cells rather than having those cells created externally and infused in a form of treatment know as CAR T-cell therapy.

As part of another of the funded projects, David Thompson at the Vancouver Coastal Health Research Institute will conduct clinical trials for one of the worlds first genetically engineered cell replacement therapies for type 1 diabetes.

Dr. Sara Vasconcelos points to an image of vascular tissue in the laboratory at Toronto General Hospital where they engineer cell and tissue regeneration.Christopher Katsarov/The Globe and Mail

The diversity of the projects highlights the increasing prominence of stem cells in multiple domains of health research, an area where Canada has a long track record of success ever since University of Toronto researchers James Till and Ernest McCullough established the existence of stem cells cells which can differentiate into more specialized types in bone marrow in 1961.

Tania Bubela, dean of health sciences at Simon Fraser University in Burnaby, B.C., said the kind of funding the Stem Cell Network provides helps bridge a crucial gap between fundamental laboratory research and proven therapies for patients.

What weve realized over time is that where you get public sector investments to close the funding gap is exactly in that translational space from preclinical into early stage clinical trials, Dr. Bubela said. Once you have that proof that things are going to work and that they can be taken up by the health system, thats when venture capital starts to get interested.

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Heart, cancer and diabetes projects among winners of funding boost for stem cell therapies - The Globe and Mail

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Lab animalshave been an essential part of life-altering and lifesaving scientific research and discovery. But a growing number of scientists are calling for an end to their use, and pushing for new methods that can better replicate human biology instead.

Among them is biomedical researcher Dr. Charu Chandrasekera. She'sthe founder and executive director of the Canadian Centre for Alternatives to Animal Methods at the University of Windsor. Here is part of her conversation with Quirks & Quarks host Bob McDonald.

Animal testing historically has been considered a regrettable necessity in the quest to save human lives. Why do you think this is not the case?

Animals have played an integral role in science over the past century or more, to the point where we have made them the gold standard for human biology. And therein lies the problem.

Over 90 per centof drugs tested to be safe and effective in animals, fail in human clinical trials. And even the ones that make it through, they can still be withdrawn or receiveblack box warnings due to unpredicted side effects in humans. And it's not just the drugs that fail, but the drugs that we missed,like the drugs that never made it to human clinical trials because they had some irrelevant side effects in animals. They could very well been safe in humans.So we've likely missed out on many life saving, history altering medications.

Why would a drug work in an animal but not in a human?

Well, there's a very simple answer to that. We humans, we are not 70-kilogram versionsof mice, rats, guinea pigs, rabbits, cats, dogs, sheep or monkeys. We're human. We're separated by hundreds of millions of years of evolution from some of these laboratory animal species.

And it's not only just the species' differences, but there are also so many issues with the way we conduct this research. We have to induce disease by either doing surgical modifications, giving them a high-fat diet. So dietary modifications, genetic modifications, take out a gene, put in a gene, or chemically destroy their pancreas, for example, to create diabetic models. So when you're doing these experimental modifications in these animals, you're really not recreating the human disease. You are creating a version of a human disease.

What motivated you to go from doing animal research in your lab to trying to end the practice altogether?

It was the scientific failures combined with the ethical standards that I was not happy with. So I worked with animal models of heart failure. And while I was doing all these studies, my dad actually had a heart attack and he required quadruple bypass surgery. And while I was with him at the Halifax Heart Centre, I thought to myself, is the research that I'm doing going to truly help humans like my father and everybody else in this ward?

A few weeks later, when I came back to the lab, I ran into this veteran cardiovascular researcher, and he had worked on receptors similar to the ones that I was working on. And I just looked at him and I said, "Do you think these receptors were activated in my dad's heart during his heart attack?" And his response was, "How the hell would I know? We've never looked at this in the human heart."And for me, that day, it was a profound realization. It was almost like an epiphany. What am I doing this for?

Those are the reasons why we should end animal research. Let's explore some of the solutions. What are some of the alternative methods to animals in research that are being developed?

Recreating human biology in a petri dish is no easy feat. There's no single magical method that can replace all animal testing tomorrow morning. It's really all about context of use, fit for purpose. What is the biological question you're trying to answer, and in what context, and how best can we address that?

So we can use human cells and tissues from cadavers and surgical remains. We can take a diseased heart removed during transplant surgery and bring it back to life in the lab, make it beat again, infused with drugs to study cardiac physiology and cardiac toxicity. We can take just a single human cell and obtain hundreds of data points on human DNA and RNA through multiomics studies. We can engineer human tissue, create miniature organ models like organoids to recapitulated complex diseases using stem cell technologies. The field is just exploding.

Can you give me a list of some of the projects that you're working on at your centreright now?

We currently have liver, gut, kidney, lung and blood brain barrier models in development. And we have a number of projects that incorporate these tissues in different configurations to create disease in a dish, and toxicity on a chip. One of the first disease models we're creating is diabetes in a dish, and we're also doing Alzheimer's in a dish. We actually have a project designed specifically to reduce and replace toxicity testing in dogs. And we even have an eco-toxicology project where we're using fish lines to replace toxicity testing on live fish.

This is all based on evidence now. So for some of these methods that we have, we are already seeing that they are able to recapitulate these human responses. We can actually look at the data that we get from using these new technologies and compare them against existing data. But we are also seeing things like new data where we're going back and reevaluating these old drugs that failed in one system and then putting them through a human biology based system. And we're seeing that they are able to predict human biology better.

How hopeful are you that we can make this shift away from using animals in scientific research?

I'm actually very hopeful that we will be able to shift away from this animal-centred paradigm to one where human biology is the gold standard and humans are the quintessential animal model. There are scientific, innovative financial and legislative efforts happening around the world to make this happen.

The goal really is to reduce as much as possible at this point. And even if we needed to use animals, could they become the last resort that you are only using, you know, five rats, for example, for a procedure that required 400 rats before?So because of all of these efforts happening globally, I'm very hopeful.

Produced by Amanda Buckiewicz. This interview has been edited for length and clarity.

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Meet the Canadian researcher determined to take the animals out of lab testing - CBC.ca

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As previously reported by BioSpace, a group of scientists from The Babraham Institutein the United Kingdom was able to successfully rejuvenate skin cells by a full 30 years.

The research team published a study in eLife Sciences last month describing their process of using induced pluripotent stem cell (iPSC) reprogramming to reverse aging effects at the cellular level.

Study co-author Ins Milagre told BioSpace that the research process was a team effort. In Lead Author Wolf Reiks lab, she was working on cell reprogramming while a colleague focused on the epigenetic clock.

Milagre came into her research career driven by an early interest in biology. I was fascinated by biology all of my life. I had a very good biology teacher when I was in high school, she said.

She explained that she was also a huge fan of the drama series The X-Files, seeing Gillian Anderson's character, Dana Scully, as a role model. I thought that being a scientist must be very cool. This combination made me decide to go into biology.

The research teams original hypothesis came from knowing that we can easily program cells to be zero years of age. No matter what age they are in the beginning, the cells normally reprogram back to embryonic age, or zero years of age.

Though reprogrammed embryonic cells are free of gradual aging decline, they lack identity and thus function. The research team began to consider what would happen if they could get the cells to only partially rejuvenate.

With embryonic cells, downstream applications can be a problem. We thought that maybe we could just rejuvenate the cells and then coax them back into being the cell of origin, Milagre explained. At first, the idea was casually discussed over happy hour, but then the team found that preliminary experiments yielded promising results.

They utilized Yamanaka factors (Oct4, Sox2, Klf4, c-Myc), which are typically used to differentiate cells into the embryonic stem cell stage. Instead of allowing the full time that it takes for cells to get to the embryonic life stage, we decided to stop the reprogramming process halfway through, Milagre said.

By doing this, we were able to get the cells to a younger age. They were easily reverted back to the original cell type, which in our case, were skin cells. Pausing the process in the middle allowed the cells to become a younger version of the same cell type. The researchers named the novel method maturation phase transient reprogramming (MPTR).

What I find very exciting about this study is that we showed that it's possible to rejuvenate cells, she said. Though the Yamanaka factors have been used in other labs, the Babraham Institute team was the first to rejuvenate cells by a full 30 years.

Courtesy of the Babraham Institute

The scientists observed several benefits of the functionally younger cells. The skin cells were better able to produce collagen, and they were responding better to wound healing sites, Milagre said. The above photo depicts the collagen levels of the skin cells before and after rejuvenation. On the left are the original 53-year-old skin cells, and on the right are the reprogrammed cells. The collagen levels are depicted in red.

Milagre noted that the study is very preliminary, with much more research to be completed before the technology is safe and available. We only tested this in skin cells, so we don't know if this is also possible in other cell types, though we believe that it probably is based on similar work from other groups.

Another element that must be studied is how the technology will work without using the same viral vectors. We need to make a safer technology to do this. As a proof of principle, we showed that it's possible to rejuvenate cells by 30 years. Now, we need to do more research to be able to eventually move this technology into a more clinical setting.

Once the technology is safe and ready, Milagre noted that many downstream applications could be possible. We can think about trying to tackle neurodegenerative and degenerative disorders as well as ameliorating some aging effects. If we can get cells to be functionally younger, even if we don't expand peoples lives, we might be able to give people a better quality of life.

Reik explained in an earlier article that the findings could eventually lead to targeting specific genes that would be able to rejuvenate without any reprogramming. Milagre said that Yamanaka factors are working as pioneers that can start new gene expression programs. If we understand which genes are being activated downstream, we can eventually think about modulating these genes. We can try switching on a minimum number of effector genes. This would be a way to overcome using viral vectors.

Though potential future benefits of the findings are a long way off, the team is still considering the people they may help down the line. We hope the technology will help people live better lives without diseases, or without the consequences of a disease even if they still have it, Milagre said.

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Scientists Rejuvenate Skin Cells by 30 Years, with Pioneering Potential - BioSpace

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Saahil Joshi, age 17, Crystal Springs Uplands School, Hillsborough, Calif.: Too Many Cooks Spoil the Broth: The Science and Future of Drug-Drug Interactions

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Chloe Lee, age 14, Korea International School Pangyo Campus, Gyeonggi-do, Korea: Do Plants Have Feelings?

Seungjae (Andy) Lee, age 13, Hong Kong International School, Tai Tam, Hong Kong: Keeping Your Pet Friend Forever: Is Cloning a Soul Possible?

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Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest - The New York Times

Skin Stem Cells Comments Off on Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest – The New York Times | May 13th, 2022

We all love trying out new skincare products that give our skin that supple plump and glow. Many of us also use anti-ageing and skin firming products to help reduce those stubborn wrinkles, pigmentation and fine lines. Ever heard the saying, An apple a day, keeps the doctor away? Now, what if we told you that this apple can help your skin without you actually having to eat it? Got you wondering how now, did we?Until several years ago, the tart, unappealing variant of the Swiss-grown Uttwiler Sptlauber apples, wasnt proving to add any value in terms of offering. This was until some scientists discovered the unusual longevity of the stem cells that kept these apples alive months after other apples shriveled and fell off their trees. What are stem cells, you ask? Stem cells are extremely unique in a way that they have the ability to go through numerous cycles and cell divisions while maintaining the undifferentiated state. Essentially, stem cells are capable of self-renewal and can transform themselves into other cell types of the same tissue. One of their primary roles is to replenish dying cells and regenerate damaged tissue. Stem cells provide the ability for species to renew and repair themselves. Plants are rooted in the ground and have to survive extreme weather changes, therefore their stem cells contain much stronger antioxidant contents than those of humans cells.

But how does this help your skin? Heres a list of the goodness that Swiss apple stem cells can have on your skin.

The high antioxidant found in plant stem cells supports the skin in combating free radicals that would otherwise cause skin damage. They give your skin the tools to protect itself, offering immense anti-ageing and anti-inflammatory benefits. The boost of antioxidants and amino acids helps boost collagen production and keeps your skin radiant and youthful.

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Have you heard of the goodness of Swiss apple stem cells? - Times of India

Skin Stem Cells Comments Off on Have you heard of the goodness of Swiss apple stem cells? – Times of India | May 13th, 2022

In 1996, Dolly the sheep made headlines around the world after becoming the first mammal to be successfully cloned from an adult cell. Many commentators thought this would catalyze a golden age of cloning, with numerous voices speculating that the first human clone must surely be just a few years away.

Some people suggested that human clones could play a role in eradicating genetic diseases, while others considered that the cloning process could, eventually, eliminate birth defects (despite research by a group of French scientists in 1999 finding that cloning may actually increase the risk of birth defects).

There have been various claims all unfounded, it is important to add of successful human cloning progams since the success of Dolly. In 2002, Brigitte Boisselier, a French chemist and devout supporter of Ralism a UFO religion based on the idea that aliens created humanity claimed that she and a team of scientists had successfully delivered the first cloned human, whom she named Eve.

However, Boisselier was unwilling or indeed unable to provide any evidence, and so it is widely believed to be a hoax.

So why, almost 30 years on from Dolly, haven't humans been cloned yet? Is it primarily for ethical reasons, are there technological barriers, or is it simply not worth doing?

Related: What are the alternatives to animal testing?

"Cloning" is a broad term, given it can be used to describe a range of processes and approaches, but the aim is always to produce "genetically identical copies of a biological entity," according to the National Human Genome Research Institute (NHGRI).

Any attempted human cloning would most likely utilize "reproductive cloning" techniques an approach in which a "mature somatic cell," most probably a skin cell, would be used, according to NHGRI. The DNA extracted from this cell would be placed into the egg cell of a donor that has "had its own DNA-containing nucleus removed."

The egg would then begin to develop in a test tube before being "implanted into the womb of an adult female," according to NHGRI.

However, while scientists have cloned many mammals, including cattle, goats, rabbits and cats, humans have not made the list.

"I think there is no good reason to make [human] clones," Hank Greely, a professor of law and genetics at Stanford University who specializes in ethical, legal and social issues arising from advances in the biosciences, told Live Science in an email.

"Human cloning is a particularly dramatic action, and was one of the topics that helped launch American bioethics," Greely added.

The ethical concerns around human cloning are many and varied. According to Britannica, the potential issues encompass "psychological, social and physiological risks." These include the idea that cloning could lead to a "very high likelihood" of loss of life, as well as concerns around cloning being used by supporters of eugenics. Furthermore, according to Britannica, cloning could be deemed to violate "principles of human dignity, freedom and equality."

In addition, the cloning of mammals has historically resulted in extremely high rates of death and developmental abnormalities in the clones, Live Science previously reported.

Another core issue with human cloning is that, rather than creating a carbon copy of the original person, it would produce an individual with their own thoughts and opinions.

"We've all known clones identical twins are clones of each other and thus we all know that clones aren't the same person," Greely explained.

A human clone, Greely continued, would only have the same genetic makeup as someone else they would not share other things such as personality, morals or sense of humor: these would be unique to both parties.

People are, as we well know, far more than simply a product of their DNA. While it is possible to reproduce genetic material, it is not possible to exactly replicate living environments, create an identical upbringing, or have two people encounter the same life experiences.

So, if scientists were to clone a human, would there be any benefits, scientific or otherwise?

"There are none that we should be willing to consider," Greely said, emphasizing that the ethical concerns would be impossible to overlook.

However, if moral considerations were removed entirely from the equation, then "one theoretical benefit would be to create genetically identical humans for research purposes," Greely said, though he was keen to reaffirm his view that this should be thought of as "an ethical non-starter."

Greely also stated that, regardless of his own personal opinion, some of the potential benefits associated with cloning humans have, to a certain degree, been made redundant by other scientific developments.

"The idea of using cloned embryos for purposes other than making babies, for example producing human embryonic stem cells identical to a donor's cells, was widely discussed in the early 2000s," he said, but this line of research became irrelevant and has subsequently not been expanded upon post-2006, the year so-called induced pluripotent stem cells (iPSCs) were discovered. These are "adult" cells that have been reprogrammed to resemble cells in early development.

Shinya Yamanaka, a Japanese stem cell researcher and 2012 Nobel Prize winner, made the discovery when he "worked out how to return adult mouse cells to an embryonic-like state using just four genetic factors," according to an article in Nature. The following year, Yamanaka, alongside renowned American biologist James Thompson, managed to do the same with human cells.

When iPSCs are "reprogrammed back into an embryonic-like pluripotent state," they enable the "development of an unlimited source of any type of human cell needed for therapeutic purposes," according to the Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles.

Therefore, instead of using embryos, "we can effectively do the same thing with skin cells," Greely said.

This development in iPSC technology essentially rendered the concept of using cloned embryos both unnecessary and scientifically inferior.

Related: What is the most genetically diverse species?

Nowadays, iPSCs can be used for research in disease modeling, medicinal drug discovery and regenerative medicine, according to a 2015 paper published in the journal Frontiers in Cell and Developmental Biology.

Additionally, Greely also suggested that human cloning may simply no longer be a "sexy" area of scientific study, which could also explain why it has seen very little development in recent years.

He pointed out that human germline genome editing is now a more interesting topic in the public's mind, with many curious about the concept of creating "super babies," for example. Germline editing, or germline engineering, is a process, or series of processes, that create permanent changes to an individuals genome. These alterations, when introduced effectively, become heritable, meaning they will be handed down from parent to child.

Such editing is controversial and yet to be fully understood. In 2018, the Council of Europe Committee on Bioethics, which represents 47 European states, released a statement saying that "ethics and human rights must guide any use of genome editing technologies in human beings," adding that "the application of genome editing technologies to human embryos raises many ethical, social and safety issues, particularly from any modification of the human genome which could be passed on to future generations."

However, the council also noted that there is "strong support" for using such engineering and editing technologies to better understand "the causes of diseases and their future treatment," noting that they offer "considerable potential for research in this field and to improve human health."

George Church, a geneticist and molecular engineer at Harvard University, supports Greely's assertion that germline editing is likely to garner more scientific interest in the future, especially when compared with "conventional" cloning.

"Cloning-based germline editing is typically more precise, can involve more genes, and has more efficient delivery to all cells than somatic genome editing," he told Live Science.

However, Church was keen to urge caution, and admitted that such editing has not yet been mastered.

"Potential drawbacks to address include safety, efficacy and equitable access for all," he concluded.

Originally published on Live Science.

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Why haven't we cloned a human yet? - Livescience.com

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