New York, July 1 : A team of US scientists, led by an Indian-origin researcher revealed that SARS-CoV-2 (coronavirus), the virus behind Covid-19, can infect heart cells in a lab dish.

This suggests it may be possible for heart cells in Covid-19 patients to be directly infected by the virus.

The discovery, published today in the journal Cell Reports Medicine, was made using heart muscle cells that were produced by stem cell technology.

We not only uncovered that these stem cell-derived heart cells are susceptible to infection by a novel coronavirus, but that the virus can also quickly divide within the heart muscle cells, said study researcher Arun Sharma from the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US.

Even more significant, the infected heart cells showed changes in their ability to beat after 72 hours of infection, Sharma added.Although many COVID-19 patients experience heart problems, the reasons remain unclear. Pre-existing cardiac conditions or inflammation and oxygen deprivation resulting from the infection have all been implicated.

But there has until now been only limited evidence the SARS-CoV-2 virus directly infects the individual muscle cells of the heart.The study also demonstrated human stem cell-derived heart cells infected by SARS-CoV-2 change their gene expression profile.This offers further confirmation the cells can be actively infected by the virus and activate innate cellular defence mechanisms in an effort to help clear-out the virus.

This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmia, heart failure and viral myocarditis, said study co-author Clive Svendsen.

While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in Covid-19, Svendsen added.

Researchers also found that treatment with an ACE2 antibody was able to blunt viral replication on stem cell-derived heart cells, suggesting that the ACE2 receptor could be used by SARS-CoV-2 to enter human heart muscle cells.

By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell, said Sharma. This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection, he explained.

The study used human induced pluripotent stem cells (iPSCs), a type of stem cell that is created in the lab from a persons blood or skin cells. IPSCs can make any cell type found in the body, each one carrying the DNA of the individual. This work illustrates the power of being able to study human tissue in a dish, the authors wrote.

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New York, July 1 : A team of US scientists, led by an Indian-origin researcher revealed that SARS-CoV-2 (coronavirus), the virus behind Covid-19, can infect heart cells in a lab dish.

This suggests it may be possible for heart cells in Covid-19 patients to be directly infected by the virus.

The discovery, published today in the journal Cell Reports Medicine, was made using heart muscle cells that were produced by stem cell technology.

We not only uncovered that these stem cell-derived heart cells are susceptible to infection by a novel coronavirus, but that the virus can also quickly divide within the heart muscle cells, said study researcher Arun Sharma from the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US.

Even more significant, the infected heart cells showed changes in their ability to beat after 72 hours of infection, Sharma added.Although many COVID-19 patients experience heart problems, the reasons remain unclear. Pre-existing cardiac conditions or inflammation and oxygen deprivation resulting from the infection have all been implicated.

But there has until now been only limited evidence the SARS-CoV-2 virus directly infects the individual muscle cells of the heart.The study also demonstrated human stem cell-derived heart cells infected by SARS-CoV-2 change their gene expression profile.This offers further confirmation the cells can be actively infected by the virus and activate innate cellular defence mechanisms in an effort to help clear-out the virus.

This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmia, heart failure and viral myocarditis, said study co-author Clive Svendsen.

While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in Covid-19, Svendsen added.

Researchers also found that treatment with an ACE2 antibody was able to blunt viral replication on stem cell-derived heart cells, suggesting that the ACE2 receptor could be used by SARS-CoV-2 to enter human heart muscle cells.

By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell, said Sharma. This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection, he explained.

The study used human induced pluripotent stem cells (iPSCs), a type of stem cell that is created in the lab from a persons blood or skin cells. IPSCs can make any cell type found in the body, each one carrying the DNA of the individual. This work illustrates the power of being able to study human tissue in a dish, the authors wrote.

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Coronavirus: WHO warns the worst is yet to come - WeForNews

Los Angeles, Jul 1 (PTI) Researchers, including those of Indian-origin, have shown that the novel coronavirus can infect lab-grown cardiac muscle cells, indicating it may be possible for the virus to directly cause heart infection in COVID-19 patients.

The study, published in the journal Cell Reports Medicine, was based on experiments conducted in lab-grown heart muscle cells which were produced from unspecialised human stem cells.

"We not only uncovered that these stem cell-derived heart cells are susceptible to infection by novel coronavirus, but that the virus can also quickly divide within the heart muscle cells," said study co-author Arun Sharma from the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US.

"Even more significant, the infected heart cells showed changes in their ability to beat after 72 hours of infection," Sharma said.

Although many COVID-19 patients experience heart problems, the scientists said the reasons for these symptoms are not entirely clear.

They said pre-existing cardiac conditions, or inflammation and oxygen deprivation that result from the infection have all been implicated.

According to the scientists, there is only limited evidence available that the novel coronavirus, SARS-CoV-2, directly infects individual muscle cells of the heart.

The current study showed that SARS-CoV-2 can infect heart cells derived from human stem-cells and change how the genes in these cells helped make proteins.

Based on this observation, the scientists confirmed that human heart cells can be actively infected by the virus, activating innate cellular "defense mechanisms" in an effort to help clear out the virus.

Citing the limitations of the study, they said these findings are not a perfect replicate of what is happening in the human body since the research was carried out in lab-grown heart cells.

However, this knowledge may help investigators use stem cell-derived heart cells as a screening platform to identify new antiviral compounds that could alleviate viral infection of the heart, believes study co-author Clive Svendsen.

"This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmias, heart failure and viral myocarditis," said Svendsen, director of the Regenerative Medicine Institute.

"While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID-19," Svendsen said.

The scientists also found that treatment with an antibody protein could lock onto the human cell surface receptor ACE2 -- a known SARS-CoV-2 ''gateway'' into cells.

According to the researchers, the antibody treatment was able to blunt viral replication on the lab-grown heart cells, suggesting that the ACE2 receptor could be used by the virus to enter human heart muscle cells.

"By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell," Sharma said.

"This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection," he added.

In the study, the researchers also used human induced pluripotent stem cells, or iPSCs, which are a type of undifferentiated cells grown in the lab from a person''s blood or skin cells.

They said iPSCs can make any cell type found in the body, each one carrying the genetic material of the individual.

According to the scientists, tissue-specific cells created in this way are used for research, and for creating and testing potential disease treatments.

"It is plausible that direct infection of cardiac muscle cells may contribute to COVID-related heart disease," said Eduardo Marban, executive director of the Smidt Heart Institute in the US, and study co-author.

"This key experimental system could be useful to understand the differences in disease processes of related coronaviral pathogens, SARS and MERS," said Vaithilingaraja Arumugaswami, another co-author of the study from the University of California Los Angeles in the US. PTI VISVIS

Disclaimer :- This story has not been edited by Outlook staff and is auto-generated from news agency feeds. Source: PTI

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Coronavirus may infect heart cells of COVID-19 patients, scientists say - Outlook India

Cardiosphere-Derived Cells

The formation of cardiospheres from human and murine heart tissue was first described in 2004 by Messina and coworkers [16]. It was demonstrated that, when placed in adherent plates, heart explants generated a layer of fibroblast-like cells over which small, phase-bright cells migrated. These phase-bright cells were collected and transferred to nonadherent plates where they originated three-dimensional structures named cardiospheres. Cardiospheres were clonogenic and when co-cultured with rat neonatal cardiomyocytes expressed troponin I and connexin 43. Additionally, there was visual evidence that cardiospheres showed synchronous contractions with cardiomyocytes. When transplanted into infarcted hearts, these cells started to express myosin heavy chain as well as -smooth muscle actin and platelet endothelial cell adhesion molecule, which resulted in functional improvement. Curiously, when the expression of surface molecules was analyzed by flow cytometry, cardiospheres showed a 25% expression of c-kit. Thus, it is possible that c-kit+ cells contribute to the characteristics observed in cardiospheres, explaining the similar findings between these two cardiac progenitor/stem cell types.

However, it was only in 2007 that Marbns group described cardiosphere-derived cells (CDCs) [19]. They slightly changed Messinas protocol by placing cardiospheres in adherent plates where cells were grown in monolayers instead of three-dimensional structures. The advantage of this step was that cell expansion in monolayers was easier and faster, which would facilitate future clinical use. Flow cytometry showed that c-kit expression was still present in similar levels to those described by Messina and coworkers. Additionally, high expression levels of CD105 and CD90 were found, indicating a mesenchymal phenotype. When co-cultured with rat neonatal cardiomyocytes, CDCs presented spontaneous intracellular calcium transients and action potentials, as well as INa, IK1 and ICa,L currents. In vivo, injection of CDCs in acute myocardial infarctions (MI) prevented further ejection fraction deterioration 3 weeks after MI when compared to placebo and fibroblast injected mice. In 2009, Marbns group also reported functional benefit and reduction of infarct size in a porcine animal model after CDC injection [37], a preclinical model that prompted a phase I clinical trial (CADUCEUS, ClinicalTrials.gov, Identifier NCT00893360).

Nonetheless, the usage of cardiospheres as a source of cardiac stem cells has been refuted. Andersen and coworkers showed that even though cardiospheres can be produced from heart specimens, they do not hold cardiomyogenic potential and simply represent aggregated fibroblasts [38]. This group also found cells that expressed cardiac contractile proteins, such as myosin heavy chain and troponin T, in cardiospheres. However, the findings were attributed to the presence of contaminating heart tissue fragments in the explant-derived cell suspension. By adding a filtration step in which explant-derived cells were passed through cell strainers prior to cardiosphere formation, the presence of cells expressing cardiac contractile proteins was eliminated. In addition, this group showed that phase-bright cells were of hematopoietic origin and did not organize into spheric structures, a characteristic attributed to the fibroblast-like cells.

In response to Andersens findings, Marbns group published a revalidation of the CDC isolation method [39]. Using a strategy identical to the one described by Hsieh and colleagues [8], cardiomyocytes were irreversibly labeled with GFP after a tamoxifen pulse (see Fig. 8.1). Isolation of CDCs from these transgenic mouse hearts did not reveal the presence of GFP+ cells, refuting the possibility that cardiac differentiation of CDCs was due to the presence of contaminating myocardial tissue fragments. Additionally, they reported that cardiospheres were consistently negative for CD45, indicating that CDCs do not contain cells of hematopoietic origin. The authors also emphasized that Andersen and coworkers used different isolation protocols, which could justify the discrepancies found in results.

Even though they demonstrated that CDCs expressed myosin heavy chain after transplantation into myocardial infarctions in mice [17], indicating that cardiomyogenic differentiation was possible in vivo, an additional mechanism was proposed to explain the improvement in cardiac function. Chimenti and colleagues studied the relative roles of direct regeneration versus paracrine effects promoted by human CDCs in a mouse infarction model [40]. The paracrine hypothesis has been used frequently to explain the beneficial effects observed with several types of adult stem cells or bone marrowderived cells used in cell therapy experiments. According to this hypothesis, stem cells could act secreting signaling molecules, which may influence cardiomyocyte survival and angiogenesis and could also recruit endogenous cardiac stem cells. Chimenti and coworkers demonstrated that CDCs secrete high levels of insulin growth factor-1 (IGF-1), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF). Moreover, using in vivo bioluminescence assays, the authors showed that no cells could be found in the heart 1 week after injection, even though functional improvement persisted until 3 weeks post-MI. Therefore, it seems that cell persistence is not important for functional improvement, strengthening the paracrine hypothesis. To address this issue, the authors quantified capillary density and viable myocardium analyzing the contributions of human (injected) and mouse (endogenous) cells to each of these variables 1-week post-MI [40]. They found that, for both variables, the contribution of endogenous cells was more prominent than that of injected cells. Hence, the release of factors seems to be more important than direct regeneration in the improvement of cardiac function after cell therapy with CDCs.

Recently, results of a phase I clinical trial using CDCs were published [41]. The safety of autologous intracoronary delivery of CDCs to patients 1.5 to 3 months after MI was evaluated. Cells were obtained from endomyocardial biopsies and cultured according to the protocols previously established by Eduardo Marbns group. Patients with a recent MI (less than 4 weeks) and left ventricular ejection fraction ranging from 25% to 45% were eligible for inclusion. Twelve months after cell therapy, patients treated with CDCs had a 12.3% decrease in scar size, whereas the control group had a 2.2% reduction, as measured by late enhancement after gadolinium MRI. However, no differences were detected in ejection fraction between cell-treated and control groups. It is important to note that this was a safety study; therefore, phase II double-blinded placebo-controlled clinical trials still need to be performed to access efficacy of therapy with CDCs in humans. Additionally, a more thorough cell biologic characterization of CDCs is required to understand provenience, molecular identity, and mechanism of action of these cells as potential cardioprotective agents.

Link:
Cardiac Stem Cell - an overview | ScienceDirect Topics

Febrero 2013

James T. Willerson, MD

James T. Willerson, MD,Texas Heart Institute

Heart and vascular disease (or cardiovascular disease, CVD) are the leading causes of death and disability in the world, despite a large proportion of it being preventable.

In the US alone, 82.6 million Americans have some form of CVD. Someone dies from CVD every 33 seconds. More than 40,000 children are born each year with a congenital heart defect.

One of the most promising new avenues for CVD treatment is the use of adult stem cells, to help heal and regenerate damaged hearts.

How can stem cells help the heart?

Stem cells are actually part of our natural circulating rescue system. They travel out of the bone marrow and patrol the circulation system looking for areas of injury to repair. We also have resident stem cells in every organ of the body.

Our first-in-the-world stem cell research at the the Stem Cell Center of the Texas Heart Institute, and subsequent clinical trials in humans, have shown that a patient's own stem cells, harvested from their bone marrow, can help generate new heart muscle tissues and blood vessels in hearts damaged by heart attacks or severe heart failure.

Advances in Stem Cells

After years of study, we have found that when people reach their early 60s, and they begin to have health issues with their bodies, their stem cells also lose their restorative powers. Subsequent research has shown, however, that certain specific cells can be taken from the body fat or bone marrow of healthy young individuals and may be used therapeutically in older patients without adverse immunological reaction. Clinical trials are ongoing and we are constantly learning more about this.

As a result of this work, the National Heart Lung and Blood Institute has established a nationwide consortium of leading medical and research institutions, the Cardiovascular Cell Therapy Research Network (CCTRN), to carry cardiac cell therapy research forward. We are very optimistic about the future of this type of stem cell therapy.

Building New Organs and Reversing Disease

Another area of great promise is the emerging field of regenerative medicine. Dr. Doris Taylor recently joined the Texas Heart Institute as Director of Regenerative Medicine Research. Through her pioneering work, we now have the capability to deplete animal and human hearts of all of their cellular structure and regenerate the "decellularized" scaffolds into healthy organs by the infusion of stem cells. These methods also work on other organs in the body. Many believe that these "bioartificial" organs are the early steps toward our ability to grow new organs for people using their own adult stem cells. We are optimistic that the technology will allow us to begin safe clinical trials in humans within only a few years.

In sum, many advances in stem cells, genetics, and regenerative medicine hold great promise and these fields are advancing rapidly. The next decade or more will undoubtedly be a golden age for progress. We are determined to push the field forward until heart and vascular disease are a thing of the past and our children have a more heart-healthy future ahead of them.

James T. Willerson, MD, is a living legend in cardiovascular medicine. He is the President and Medical Director of the Texas Heart Institute, and the immediate past President of the University of Texas Health Science Center in Houston. Dr. Willerson is a native Texan; he attend UT Austin, Baylor College of Medicine, Harvard Medical School, and trained at Massachusetts General Hospital in Boston. Dr. Willerson has received numerous honors and awards, including the Gold Heart Award, the highest award from the American Heart Association. He has been elected a Fellow in the Royal Society of Medicine of the UK, and made an Honorary Member of the Societies of Cardiology in Peru, Spain, Greece, Venezuela, and Chile. Dr. Willerson is currently President of the International Academy of Cardiovascular Sciences. There is also a swimming scholarship named for him at UT Austin.

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Stem Cells for Cardiac Patients

Regenerative Medicine Market: Snapshot

Regenerative medicine is a part of translational research in the fields of molecular biology and tissue engineering. This type of medicine involves replacing and regenerating human cells, organs, and tissues with the help of specific processes. Doing this may involve a partial or complete reengineering of human cells so that they start to function normally.

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Regenerative medicine also involves the attempts to grow tissues and organs in a laboratory environment, wherein they can be put in a body that cannot heal a particular part. Such implants are mainly preferred to be derived from the patients own tissues and cells, particularly stem cells. Looking at the promising nature of stem cells to heal and regenerative various parts of the body, this field is certainly expected to see a bright future. Doing this can help avoid opting for organ donation, thus saving costs. Some healthcare centers might showcase a shortage of organ donations, and this is where tissues regenerated using patients own cells are highly helpful.

There are several source materials from which regeneration can be facilitated. Extracellular matrix materials are commonly used source substances all over the globe. They are mainly used for reconstructive surgery, chronic wound healing, and orthopedic surgeries. In recent times, these materials have also been used in heart surgeries, specifically aimed at repairing damaged portions.

Cells derived from the umbilical cord also have the potential to be used as source material for bringing about regeneration in a patient. A vast research has also been conducted in this context. Treatment of diabetes, organ failure, and other chronic diseases is highly possible by using cord blood cells. Apart from these cells, Whartons jelly and cord lining have also been shortlisted as possible sources for mesenchymal stem cells. Extensive research has conducted to study how these cells can be used to treat lung diseases, lung injury, leukemia, liver diseases, diabetes, and immunity-based disorders, among others.

Global Regenerative Medicine Market: Overview

The global market for regenerative medicine market is expected to grow at a significant pace throughout the forecast period. The rising preference of patients for personalized medicines and the advancements in technology are estimated to accelerate the growth of the global regenerative medicine market in the next few years. As a result, this market is likely to witness a healthy growth and attract a large number of players in the next few years. The development of novel regenerative medicine is estimated to benefit the key players and supplement the markets growth in the near future.

Global Regenerative Medicine Market: Key Trends

The rising prevalence of chronic diseases and the rising focus on cell therapy products are the key factors that are estimated to fuel the growth of the global regenerative medicine market in the next few years. In addition, the increasing funding by government bodies and development of new and innovative products are anticipated to supplement the growth of the overall market in the next few years.

On the flip side, the ethical challenges in the stem cell research are likely to restrict the growth of the global regenerative medicine market throughout the forecast period. In addition, the stringent regulatory rules and regulations are predicted to impact the approvals of new products, thus hampering the growth of the overall market in the near future.

Global Regenerative Medicine Market: Market Potential

The growing demand for organ transplantation across the globe is anticipated to boost the demand for regenerative medicines in the next few years. In addition, the rapid growth in the geriatric population and the significant rise in the global healthcare expenditure is predicted to encourage the growth of the market. The presence of a strong pipeline is likely to contribute towards the markets growth in the near future.

Global Regenerative Medicine Market: Regional Outlook

In the past few years, North America led the global regenerative medicine market and is likely to remain in the topmost position throughout the forecast period. This region is expected to account for a massive share of the global market, owing to the rising prevalence of cancer, cardiac diseases, and autoimmunity. In addition, the rising demand for regenerative medicines from the U.S. and the rising government funding are some of the other key aspects that are likely to fuel the growth of the North America market in the near future.

Furthermore, Asia Pacific is expected to register a substantial growth rate in the next few years. The high growth of this region can be attributed to the availability of funding for research and the development of research centers. In addition, the increasing contribution from India, China, and Japan is likely to supplement the growth of the market in the near future.

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Global Regenerative Medicine Market: Competitive Analysis

The global market for regenerative medicines is extremely fragmented and competitive in nature, thanks to the presence of a large number of players operating in it. In order to gain a competitive edge in the global market, the key players in the market are focusing on technological developments and research and development activities. In addition, the rising number of mergers and acquisitions and collaborations is likely to benefit the prominent players in the market and encourage the overall growth in the next few years.

Some of the key players operating in the regenerative medicine market across the globe areVericel Corporation, Japan Tissue Engineering Co., Ltd., Stryker Corporation, Acelity L.P. Inc. (KCI Licensing), Organogenesis Inc., Medtronic PLC, Cook Biotech Incorporated, Osiris Therapeutics, Inc., Integra Lifesciences Corporation, and Nuvasive, Inc.A large number of players are anticipated to enter the global market throughout the forecast period.

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Regenerative Medicine Market Analysis Growth Demand, Key Players, Share Size, and Forecast To 2025 - 3rd Watch News

On February 67, 2020, the Simons Foundation Autism Research Initiative (SFARI) convened a two-day workshop to explore the possibility of gene therapies for autism spectrum disorder (ASD), a neurodevelopmental condition associated with changes in over 100 genes. Inspired by the recent, stunning successes of gene therapy for the fatal neuromuscular disorder spinal muscular atrophy (SMA)1, and by the accumulation of genes confidently associated with ASD2, SFARI welcomed a diverse collection of researchers to begin to think about whether a similar approach could be taken for ASD. Because gene therapy attempts to fix what is broken at the level of a causative gene, it would offer a more direct and imminent strategy than mitigation of the many and as yet mostly unclear downstream effects of a damaged gene.

The workshop was organized in 20 talks and several discussion panels, which tackled many outstanding issues, including how to choose candidate target genes and predict outcomes; how to optimize vectors for gene delivery; how to decide when to intervene; which animal models to develop; how to find appropriate endpoints for clinical trials and understand the available regulatory pathways. SFARI also raised the question of how its funding might best propel gene therapy efforts amid the emerging, complex ecosystem of academic laboratories, biotech companies, and pharmaceutical industries.

Even the opportunity to have this discussion is very rewarding, said SFARI Investigator Matthew State of the University of California, San Francisco (UCSF), one of the investigators who directed teams of geneticists to analyze the Simons Simplex Collection (SSC).

These efforts have offered up multiple potentially feasible therapeutic targets. Though rare, de novo disruptive mutations in the highest confidence ASD genes often result in severe impairment characterized not only by social difficulties, but also by intellectual disability and seizures. The combination of a single gene mutation of large effect coupled with particularly severe outcomes that include ASD are likely to offer the most immediate targets for gene therapy. For now, this leaves out a large number of individuals with autism for whom genetic causes are not yet known and are likely the result of a combination of many small effect alleles across a large number of genes.

Highlights from talks and discussion panel, chaired by Rick Lifton of Rockefeller University

In the first talk of the workshop, State brought the group up to speed on ASD genomics. The most recent tally from exome-sequencing in simplex cases of ASD highlighted 102 genes in which rare mutations confer individually large risks2. In contrast, the task of identifying common variants carrying very small risks remains quite challenging, with less than a half dozen alleles so far identified with confidence3. The rare, disruptive mutations that result in loss of function of one gene copy are an attractive focus for gene therapy because of the tractability of targeting a single spot in the genome per individual and because, in the vast majority of cases, there remains a single unchanged allele. This points to ways to boost gene and/or protein expression back toward the normal state by leveraging the unaffected copy. But both the limited number of cases known so far combined with the possibility that different mutations to the same gene may have different effects complicate thinking about how to prioritize targets for gene therapy.

State made several points that were continually touched on throughout the workshop. Many ASD genes are highly expressed during midfetal development in the cortex, and additional experiments will need to determine whether and how long a window of opportunity may be present for successful gene therapy postnatally. Given the relatively small number of people with these conditions, new clinical trial designs are needed that dont rely on comparisons between large control and intervention groups (see also Bryan Kings talk below).

Beyond the gene-crippling mutations found in the exome, disruptions to transcription may also dramatically raise risk for autism and may be corrected with a type of gene therapy using ASOs. SFARI Investigator Stephan Sanders of UCSF focused on the role of splicing, the process by which an initial transcript is turned into messenger RNA by removal of introns and joining together of exons. Splicing is disrupted in at least 1.5 percent of individuals with ASD4, and possibly many more, as suggested by transcript irregularities found in postmortem autism brain5. Sanders described Illuminas Splice AI project in which machine-learning helps predict noncoding variants that can alter splicing, including those beyond typical splice sites found near a gene6. As a result of incorporating sequence information around and between splice sites, this computational tool detected more mutations with predicted splice-altering consequences in people with ASD and intellectual disability than in those without the condition.

An ASO designed to bind specific portions of RNA could conceivably correct errors in transcription. ASOs have already been approved for use in other disorders in order to skip exons, retain exons or to degrade mRNA. Unlike other forms of gene therapy, ASOs do not permanently alter the genome, making it a kind of gene therapy lite. This reversibility has both disadvantages (having to re-infuse the ASO every few months) and advantages (multiple opportunities to optimize the dose and target; serious adverse effects are not permanent).

Jonathan Weissman of UCSF discussed the available toolbox for controlling gene expression developed by many different laboratories. To turn genes on or off, he has developed a method to combine CRISPR with an enzymatically inactive (dead) Cas9, which can then be coupled with a transcriptional activator (CRISPRa) or repressor (CRISPRi)7 (Figure 2). In the case of loss-of-function mutations, Weissman outlined strategies to make the remaining good allele work harder: increase transcription via CRISPRa, decrease mRNA turnover, increase translation of a good transcript via modification of upstream open reading frames (uORFs) or increase a proteins stability, possibly through small molecules acting on the ubiquitin system8. That said, the effects on a cell may be complicated. Using Perturb-Seq screens, Weissman described genetic interaction manifolds that show nonlinear mapping between genotype and single cell transcriptional phenotypes9. Additionally, Weissman summarized recent work from his laboratory that has identified large numbers of uORFs that result in polypeptides, some of which affect cellular function.

SFARI Investigator Michael Wigler of Cold Spring Harbor Laboratories echoed the idea of a gene-therapy strategy that increases expression of the remaining good copy of a gene, especially given that in his estimate, 45 percent of simplex cases of autism carried a de novo, likely disrupting variant. He also called attention to the uterine environment, especially the challenge posed by expression of paternally derived antigens in the fetus and the impact of a potential maternal immune response, and the need to understand how it interacts with de novo genetic events.

Highlights from talks and discussion panel, chaired by Arnon Rosenthal of Alector

The discussion turned to finding ways of getting genes into the central nervous system. The AAV is the darling of gene therapy, given that it does not replicate and is not known to cause disease in humans. A version that can cross the blood-brain barrier (AAV9) was used to deliver a gene replacement to children with SMA intravenously; though this effectively delivered the genetic cargo to ailing motor neurons in the spinal cord, it does not work that well at delivering genes throughout the brain.

Ben Deverman of the Stanley Center at the Broad Institute of MIT and Harvard detailed his efforts to optimize AAV for efficient transduction of brain cells through a targeted evolution process: his team engineers millions of variants in the capsid of the virus, then screens them for entry into the nervous system and transduction of neurons and glia. This has yielded versions (called AAV-PHP.B and AAV-PHP.eB) that more efficiently enter the brain10,11. One successfully delivered the MECP2 gene to the brain of a Rett syndrome mouse model, resulting in ameliorated symptoms and an extended lifespan12. Unfortunately, these viruses dont work in human cells or in all mouse strains. A quick mouse genome-wide association study (GWAS) revealed that the Ly6a gene mediates efficient blood-brain barrier crossing of AAV-PHP.B and AAV-PHP.eB13. Now his group has identified Ly6a-independent capsids that may translate better to humans. He also noted that the PHP.B vectors have tissue specificity for brain and liver.

With an estimated 87 percent of autism-associated genes raising risk through haploinsufficiency (having only one functional gene copy out of the two), SFARI Investigator Nadav Ahituv of UCSF made the case for approaches that boost expression of the remaining good copy of a gene through endogenous mechanisms a strategy he called cis-regulation therapy. This method also provides a way to work around the small four kb payload of AAV, which strains to contain cDNA of many autism genes. A recent study by his group used CRISPRa targeted at an enhancer or promoter of SIM1 and promoter of MC4R, both obesity genes, in mice. Using one AAV vector for a dCas9 joined to a transcription activator, and another AAV vector having a guide RNA targeting either a promoter or an enhancer, and a guide RNA targeting a promoter, the researchers injected the vectors together into the hypothalamus, which resulted in increased SIM1 or MC4R transcription and reversed the obesity phenotype brought on by loss of these genes14. Targeting regulatory elements had the added benefit of tissue specificity, and there seemed to be a ceiling effect for SIM1 expression, which suggested an endogenous safeguard against overexpression at work. He is now collaborating with SFARI Investigator Kevin Bender, also at UCSF, to apply this approach to the autism gene SCN2A.

Botond Roska of the Institute of Molecular and Clinical Ophthalmology in Basel, Switzerland pointed out that getting genes to the cells where they are needed is crucial when treating eye diseases. Off-target effects there can induce degeneration of healthy cells. For this reason, Roska and his group have created AAVs that target specific cell types in the retina by developing synthetic promoters that efficiently promote expression of the viruss cargo15. The promoters they designed were educated guesses based on four approaches: likely regulatory elements close to genes expressed with cell-type specificity in the retina, conserved elements close to cell typespecific genes, binding sites for cell typespecific transcription factors and open chromatin close to cell typespecific genes. Screening a library of these in mouse, macaque and human retina revealed some with high cell-type specificity (Figure 3). Importantly, macaque data predicted success in human retina much better than did mouse data. In preliminary experiments, and more relevant to gene therapy for ASD, these cell-specific vectors also had some success in mouse cortex, for example lighting up parvalbumin neurons or an apparently new type of astrocyte.

Roska also described new methods for delivery, in which nanoparticles are coated with AAV, then drawn into the brain using magnets16. This magnetophoresis technique allows a library of experimental AAVs to be tested at the same time in one monkey. Steering nanoparticles with magnets gives more control of vector placement and gene delivery. He argued that these in the future could access even deep structures of the brain.

Highlights from talks and discussion panel, chaired by Steven Hyman of the Broad Institute at MIT and Harvard

Kathy High of Spark Therapeutics reviewed the story of gene therapy for spinal muscular atrophy (SMA) type 1. Though she was not directly involved in that research, she is well aware of the regulatory atmosphere surrounding gene therapy, given that Spark Therapeutics developed the first approved AAV-delivered gene for a form of retinal dystrophy. The SMA story is a useful case study in that an ASO-based therapy (nusinersen, marketed as Spinraza), approved in 2016, set the stage for a gene-replacement therapy, marketed as Zolgensma (onasemnogene abeparvovec). Ultimately, the amount of data supporting Zolgensmas approval was modest: a Phase one dose study of 15 infants1, and an ongoing Phase three trial of 21 infants and safety data from 44 individuals. Yet the approval was helped by the dramatic results and clear endpoints: those receiving a single intravenous infusion of an AAV9 vector containing a replacement gene all remained alive at 20 months of age, whereas only 8 percent survived to that age in the natural history data, which compiles the diseases untreated course. High mentioned that maintaining product quality for gene therapeutics may prove trickier than for typical medications.

The attractive, highly customizable nature of gene therapy might have a regulatory downside in that different vector payloads, even when designed to do the same thing, could invite separate approval processes. Though not knowing how regulatory agencies would view this, High said that their perspectives are bound to evolve as more gene therapy trials are completed.

Getting to ASD-related syndromes, Bender talked about SCN2A, which encodes the sodium channel Nav1.2. SCN2A mutations in humans can be gain of function or loss of function; gain-of-function mutations are associated with early onset epilepsy, and loss-of-function mutations with intellectual disability and ASD. In a mouse model missing one copy of SCN2A, Bender and his group have discovered a role for SCN2A in action potential generation in the first week after birth, and in synaptic function and maturation afterward through regulation of dendritic excitability18 (Figure 4). Using AAV containing CRISPRa constructs developed with the Ahituv lab, the researchers successfully increased SCN2A expression, and recovered synapse function and maturity, even when done several weeks postnatally. Getting the appropriate dosage is critical since gain-of-function mutations are linked to epilepsy. However, Bender reported even when SCN2A expression increased to double normal levels, no hints of hyperexcitability appeared. We might be able to overdrive this channel as much as we want and actually may not have risk of producing an epileptic insult, he said. Next steps are to figure out the developmental windows for intervention, evaluate changes in seizure sensitivity and extend this kind of cis-regulatory approach to other ASD genes.

Angelman syndrome is another condition that attracts interest for gene therapy, in part because neurons already harbor an appropriate replacement gene. Angelman syndrome stems from mutations to the maternally inherited UBE3A gene, which is particularly damaging to neurons because they only express the maternal allele, while the paternal allele is silenced by an antisense transcript. SFARI Investigator Mark Zylka of the University of North Carolina and colleagues showed in 2011 that this paternal allele could be unsilenced with a cancer drug in a mouse model of Angelman syndrome19. Since then, three companies have built ASOs to do the same thing, and these are going into clinical trials. To get a more permanent therapeutic, Zylka has been developing CRISPR/Cas9 systems to reactivate paternal UBE3A, and preliminary experiments show that injecting this construct into the brains of embryonic mice, and then again at birth, results in brain-wide expression of paternal UBE3A and is long-lasting (at least 17 months). Zylka is now making human versions of these constructs. He later noted rare cases of mosaicism for the Angelman syndrome mutation people with 10 percent normal cells in blood have a milder phenotype20, which suggests that even inefficient transduction of a gene vector could help.

Zylka also made a case for prenatal interventions in Angelman syndrome: studies of mouse models indicate that early reinstatement of UBE3A expression in mouse embryos rescues multiple Angelman syndrome-related phenotypes, whereas later postnatal interventions rescue fewer of these21; for humans, a diagnostic, cell-based, noninvasive prenatal test will be available soon22; ultrasound-guided injections into fetal brain of nonhuman primates have been developed23; prenatal surgeries are now standard of care for spinal bifida; and intervening prenatally decreases the risk of an immunogenic response to an AAV vector or its cargo. During the discussion, it was noted that another benefit of acting early was that less AAV would be needed to transduce a much smaller brain; however, a drawback is the lack of data on Angelman syndrome development from birth to one year of age. This natural history would be necessary for understanding whether a prenatal therapy is more effective than treatment of neonates.

SFARI Investigator Guoping Feng of the Massachusetts Institute of Technology has been investigating SHANK3, a high-confidence autism risk gene linked to a severe neurodevelopmental condition called Phelan-McDermid syndrome, which is marked by intellectual disability, speech impairments, as well as ASD. SHANK3 is a scaffold protein important for organizing post-synaptic machinery in neurons. Mouse studies by Feng have shown that SHANK3 re-expression in adult mice that have developed without it can remedy some, but not all, of their phenotypes, including dendritic spine densities, neural function in the striatum and social interaction24. Furthermore, early postnatal re-expression rescued most phenotypes. This makes SHANK3 a potential candidate for gene therapy; however, it is a very large gene 5.2kb as a cDNA that is difficult to fit into a viral vector. To get around this, Fengs group has designed a smaller SHANK3 mini-gene as a substitute for the full-sized version. Preliminary experiments show that AAV delivery of the mini-gene can rescue phenotypes like anxiety, social behavior and corticostriatal synapse function in SHANK3 knockout mice. Feng also discussed his success in editing the genome in marmosets and macaques using CRISPR/Cas9 technology and showed data from a macaque model of SHANK3 dysfunction25. These models may help test gene therapy approaches and identify biomarkers of brain development closely related to the human disorder.

For people with rare conditions brought on by even rarer mutations, individualized gene therapies can provide a pathway for treatment. SFARI Investigator Timothy Yu of Boston Childrens Hospital/Harvard described his N-of-1 study in treating a girl with Batten disease, a recessive disorder in which a child progressively loses vision, speech and motor control while developing seizures. In a little over a year, an ASO that targeted her unusual splice-site mutation in the CLN7 gene was designed, developed and given intrathecally to the girl26. The lift was in negotiating with the FDA and working with private organizations, not just in the science, Yu said. After a year of treatment with the ASO (dubbed milasen after the girl, Mila), there were no serious adverse events; seizure frequency and duration had decreased (Figure 5); and possibly her decline had slowed. Though she remains blind, without intelligible speech and unable to walk on her own, she was still attentive and could respond happily to her familys voices. The highly personalized framework for this drugs approval is completely different from how medications meant for populations are approved, and it opens a regulatory can of worms, Yu said, though he added that the regulators were willing to countenance drug approval for an individuals clinical benefit.

Rett syndrome is a neurodevelopmental condition caused by mutations to the MECP2 gene that has a substantial research base in mouse models. Over 10 years ago, mouse models highlighted the possibility for therapeutics in this condition when Rett-associated phenotypes were rescued by adding back MECP2, even in adulthood27. This reversibility has spurred interest in gene therapy for Rett syndrome, but getting the MECP2 dose right is critical, said Stuart Cobb of the University of Edinburgh and Neurogene: just as too little MECP2 leads to Rett syndrome, too much also results in severe phenotypes. For this reason, it would be nice to package a replacement MECP2 gene with other regulatory elements to control its expression, but this results in constructs that do not fit into viral vectors. To make more room, Cobb and his colleagues have been able to chop away two-thirds of the MECP2, reserving two domains that interact to make a complex on DNA (Figure 6). Mice with this mini-gene are viable and have near normal phenotypes; likewise, injecting this mini-gene into MECP2-deficient mice extended their survival28. Doubling the dose, however, substantially lowered survival. Putting in safety valves to prevent overexpression is going to be quite important, he said. One idea is to add back a construct containing only the last two exons of MECP2, which is where most Rett mutations land. These would then be spliced into native transcripts (called trans-splicing), and thus their expression controlled by endogenous regulatory elements.

Underscoring the double-edged sword of MECP2 dosage, Yingyao Shao from Huda Zoghbis lab at Baylor described an MECP2 duplication syndrome (MDS) in humans, which features hypotonia, intellectual disability, epilepsy and autism. Experiments in an MDS mouse model, which carries one mouse version and one human version of MECP2, recapitulates some of the phenotypes of the human condition and can be rescued by an ASO targeting the human allele29. Shao described work to optimize the ASO for translation into humans, which involved developing a more humanized MDS model that carries two human MECP2 alleles. An acute injection of the ASO was able to knock down MECP2 expression in a dose-dependent manner in these mice, and RNA levels dropped a week after injection, with protein levels falling a week later. MECP2 target genes also normalized their expression level, and one maintained this for at least 16 weeks post-injection. The ASO also rescued behavioral phenotypes of motor coordination and fear conditioning, but not of anxiety; these corrections followed the molecular effects, and these timelines would be important to keep in mind while designing clinical trials. Shao also noted that overtreatment with the ASO resulted in Rett-associated phenotypes, but that this was reversible, which suggests that some fine-tuning of dosing in humans might be possible.

To avoid overtreatment and toxicity of any MDS-directed therapy, Mirjana Maletic-Savatic, also at Baylor, is leaving no stone unturned in a hunt for MDS biomarkers that can predict, in each individual, the safety of a particular dose and regimen. Such biomarkers would also help monitor individuals during treatment, give information about target engagement and identify candidates for a particular treatment. Anything found to be sensitive to expression levels of MECP2 could also be useful for Rett, though she noted that MECP2 levels measured in blood do not track linearly with gene copy number. Thus, because of interindividual variability, her approach is to collect a kitchen sink of data deriving composite biomarkers that accurately reflect the stage and severity of disease in a given case. She and her colleagues are collecting clinical, genetic, neurocircuitry (such as EEG and sleep waves), immunology and molecular data detected in blood, urine and CSF. These measures are also being explored in induced neurons derived from skin samples of people with MDS. She highlighted two interrelated potential biomarkers in the blood of those with this condition; both measures are downstream targets of MECP2 and are responsive to ASO treatment.

Highlights from Early detection and clinical trial issues talks and panel discussion, chaired by Paul Wang of SFARI

Coming up with objective measures of a persons status either their eligibility for a treatment, or whether the treatment has engaged with its target or even whether the treatment is effective is a real necessity in autism-related conditions, which comprise multiple interrelated behaviors. Eye-tracking methodology may provide such a marker, argued SFARI Investigator Ami Klin of Emory University. Focusing on the core social challenges of autism, Klin, Warren Jones and colleagues have been studying children as they view naturalistic social scenes to quantify their social attention patterns. This has revealed how remarkably early in development social visual learning begins and that this process is disrupted in infants later diagnosed with ASD prior to features associated with the condition appearing. By missing social cues, autism in many ways creates itself, moment by moment, Klin said. In considering gene therapy, it may be useful to know that eye looking (how much a subject looks at a persons eyes, an index of social visual engagement) in particular and social visual engagement in general are under genetic control30; that eye-tracking differences emerge as early as 26 months of age; and that homologies in social visual engagement exist between human babies and nonhuman infant primates.

In getting to a point to test gene therapies, identifying those who need them is essential. Wendy Chung of Columbia University and the Simons Foundation illustrated how diagnosis is yoked closely to therapy. To illustrate this, she described her pilot study of newborn blood spots to screen for SMA; at the start, no treatment was available, but the screen identified newborns for a clinical trial of nusinersin. Notably, the screen only cost an additional 11 cents per baby. In the three years since her pilot screen began, the FDA approved two gene therapies for SMA and the SMA screen was adopted for nationwide newborn screening. Currently she is piloting a screen for Duchenne muscular dystrophy and plans to develop a platform that will allow researchers to add other conditions. In prioritizing genetic conditions for gene therapy, she outlined some ideas for focus, such as genes resulting in phenotypes that would not be identified early without screening, those that are relatively frequent, those that are lethal or neurodegenerative, those with a treatment in clinical trials or with FDA-approved medications, and those conditions that are reversible.

In the meantime, Chung also outlined SFARIs involvement in establishing well-characterized cohorts of individuals with autism, which can help lay a groundwork for gene therapy. People with an ASD diagnosis can join SPARK (Simons Foundation Powering Autism Research for Knowledge), which collects medical, behavioral and genetic information (through analysis of DNA from saliva, at no cost to the participant). If a de novo genetic variant is found in one of ~150 genes, that person is referred to Simons Searchlight, which fosters rare conditions communities and which is also compiling natural history data on people with these mutations.

Bryan King of UCSF discussed how current trial designs for ASD were inadequate for gene therapy trials. As ASD prevalence has grown, parallel design trials with one group receiving an experimental medicine and the other a placebo are the standard, but these wont be possible for the rare conditions that are candidates for gene therapy. Also, change is hard to capture, given the malleable nature of ASD: with no intervention, diagnosis can shift between ASD and pervasive developmental disorder-not otherwise specified (PDD-NOS) in 1284 months (as defined by the DSM-IV). Current scales are subjective and may miss specific items of clinical significance. (Last year, SFARI funded four efforts to develop more sensitive outcome measures.) King outlined other pitfalls in ASD clinical trials, including significant placebo responses, inadequate sample sizes and not being specific enough when asking about adverse effects. King also mentioned improvements that may arise from just enrolling in a study, which could prompt previously housebound families to venture out with their child, which could kick off a cascade of positive effects. He reiterated how, for gene therapy, a natural history comparison group may be more appropriate, combined with solid outcome measures.

SFARI Investigator James McPartland of Yale University then underlined the need for objective biomarkers for clinical trials, for which there are currently none that are FDA qualified for ASD. As the director of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT), he works with other scientists to develop reliable biomarkers that can be scaled for use in large samples across different sites. McPartland noted a biomarker studied in the ABC-CT: an event-related potential (N170) to human faces, which is on average slower in ASD than in typically developing children. He is working on ways to make it easier for people with ASD and intellectual disabilities to participate in biomarker studies and to make them more socially naturalistic. In discussion, he mentioned he thought it would be possible to look for these kinds of biomarkers in younger children.

SFARI Investigator Shafali Jeste of the University of California, Los Angeles recounted her experience in working with children with genetic syndromes associated with neurodevelopmental conditions. Though she is asked to participate in clinical trials for these conditions, she senses the field has some work to do to be ready for these trials, particularly in those with additional challenges such as epilepsy and intellectual disability. Meaningful and measurable clinical endpoints are still insufficient, and there needs to be more ways to improve accessibility of these trials for these rare conditions. This means developing new measures, such as gait-mat technology that senses walking coordination, or EEG measures in waking and sleep, which have been applied to people with chromosome 15q11.2-13.1 duplication (dup15q) syndrome, who have severe intellectual disability and motor impairments. Jeste also emphasized that increasing remote access to some measures can make a big difference for a trial; for example, a trial of a behavioral intervention for tuberous sclerosis complex that required weekly lab visits was disappointingly under-enrolled until researchers revamped it so most of the intervention could be done remotely31.

By grappling with the challenges to gene therapy for ASD, the workshop marked out a faint road map of a way forward. As the scientific questions are answered, the regulatory and clinical trial infrastructure will need to develop apace, and coordination between private, academic and advocacy sectors will be essential. But as gene therapy for diverse human conditions continues to be explored and gene discovery in ASD continues, there is reason to believe that some forms of ASD can eventually benefit from this strategy.This workshop provided a terrific discussion about the challenges in developing targeted gene interventions and their potentially transformative effects as therapies, said John Spiro, Deputy Scientific Director of SFARI. We are grateful to all theparticipants, and SFARI looks forward to translating these discussions into focused funding decisions in the near future.

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SFARI | SFARI workshop explores challenges and opportunities of gene therapies for autism spectrum disorder - SFARI News

Stem Cell Assay Market: Snapshot

Stem cell assay refers to the procedure of measuring the potency of antineoplastic drugs, on the basis of their capability of retarding the growth of human tumor cells. The assay consists of qualitative or quantitative analysis or testing of affected tissues andtumors, wherein their toxicity, impurity, and other aspects are studied.

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With the growing number of successfulstem cell therapytreatment cases, the global market for stem cell assays will gain substantial momentum. A number of research and development projects are lending a hand to the growth of the market. For instance, the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM) has attempted to manipulate stem cells to heal eye, kidney, and heart injuries. A number of diseases such as Alzheimers, spinal cord injury, Parkinsons, diabetes, stroke, retinal disease, cancer, rheumatoid arthritis, and neurological diseases can be successfully treated via stem cell therapy. Therefore, stem cell assays will exhibit growing demand.

Another key development in the stem cell assay market is the development of innovative stem cell therapies. In April 2017, for instance, the first participant in an innovative clinical trial at the University of Wisconsin School of Medicine and Public Health was successfully treated with stem cell therapy. CardiAMP, the investigational therapy, has been designed to direct a large dose of the patients own bone-marrow cells to the point of cardiac injury, stimulating the natural healing response of the body.

Newer areas of application in medicine are being explored constantly. Consequently, stem cell assays are likely to play a key role in the formulation of treatments of a number of diseases.

Global Stem Cell Assay Market: Overview

The increasing investment in research and development of novel therapeutics owing to the rising incidence of chronic diseases has led to immense growth in the global stem cell assay market. In the next couple of years, the market is expected to spawn into a multi-billion dollar industry as healthcare sector and governments around the world increase their research spending.

The report analyzes the prevalent opportunities for the markets growth and those that companies should capitalize in the near future to strengthen their position in the market. It presents insights into the growth drivers and lists down the major restraints. Additionally, the report gauges the effect of Porters five forces on the overall stem cell assay market.

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Global Stem Cell Assay Market: Key Market Segments

For the purpose of the study, the report segments the global stem cell assay market based on various parameters. For instance, in terms of assay type, the market can be segmented into isolation and purification, viability, cell identification, differentiation, proliferation, apoptosis, and function. By kit, the market can be bifurcated into human embryonic stem cell kits and adult stem cell kits. Based on instruments, flow cytometer, cell imaging systems, automated cell counter, and micro electrode arrays could be the key market segments.

In terms of application, the market can be segmented into drug discovery and development, clinical research, and regenerative medicine and therapy. The growth witnessed across the aforementioned application segments will be influenced by the increasing incidence of chronic ailments which will translate into the rising demand for regenerative medicines. Finally, based on end users, research institutes and industry research constitute the key market segments.

The report includes a detailed assessment of the various factors influencing the markets expansion across its key segments. The ones holding the most lucrative prospects are analyzed, and the factors restraining its trajectory across key segments are also discussed at length.

Global Stem Cell Assay Market: Regional Analysis

Regionally, the market is expected to witness heightened demand in the developed countries across Europe and North America. The increasing incidence of chronic ailments and the subsequently expanding patient population are the chief drivers of the stem cell assay market in North America. Besides this, the market is also expected to witness lucrative opportunities in Asia Pacific and Rest of the World.

Global Stem Cell Assay Market: Vendor Landscape

A major inclusion in the report is the detailed assessment of the markets vendor landscape. For the purpose of the study the report therefore profiles some of the leading players having influence on the overall market dynamics. It also conducts SWOT analysis to study the strengths and weaknesses of the companies profiled and identify threats and opportunities that these enterprises are forecast to witness over the course of the reports forecast period.

Some of the most prominent enterprises operating in the global stem cell assay market are Bio-Rad Laboratories, Inc (U.S.), Thermo Fisher Scientific Inc. (U.S.), GE Healthcare (U.K.), Hemogenix Inc. (U.S.), Promega Corporation (U.S.), Bio-Techne Corporation (U.S.), Merck KGaA (Germany), STEMCELL Technologies Inc. (CA), Cell Biolabs, Inc. (U.S.), and Cellular Dynamics International, Inc. (U.S.).

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Stem Cell Assay Market In-Depth Analysis and Forecast 2017-2025 - Daily Veterans

Houston has played a significant role in boosting the nations biotech industry. While Houston is still a hotspot for energy and oil, the city is steadily becoming a burgeoning life sciences hub. In fact, the city boasted the third fastest-growing biotech community in the nation between 2014 and 2017, according to a CBRE report. Houstons biotech industry is gaining momentum due to an increase in funding as well. According to the Greater Houston Partnership, nearly $180 million in VC funding was allocated to the citys ecosystem of life sciences-related companies in 2019 alone.

Like many startups and tech companies across Houston, the citys life sciences leaders have been tackling some of the worlds most pressing issues. Whether theyre developing oncology drug candidates or advancing genomic medicine through the creation of sequencing technologies, the citys biotech organizations are pulling on decades of research and determination to transform the medical landscape on a global scale. Heres a look at 15 biotech companies in Houston making a major impact on medical research and discovery.

Founded: 2015

Focus: Canine Cancer Treatment

What they do:CAVU Biotherapiesprovides immune-based solutions to treat cancer and autoimmune diseases in dogs. The company offers an immune health monitoring service, which describes a dogs immune system through the use of a blood sample, as well as an autologous prescription product that retrains and expands a dogs T cells to recognize and fight cancer. CAVU Biotherapies ultimate aim is to use its immune-guided medicine to treat horses, cats, andeventually, humans.

Founded: 2006

Focus: Stem Cell Banking + Therapy

What they do: Founded by David Eller and Dr. Stanley Jones, Celltex Therapeutics focuses on developing stem cell therapies for a variety of conditions. The companys stem cell processing and banking methods are designed to ensure the genetic integrity and uniformity of an individuals cells in quantities necessary for therapeutic applications. Using proprietary technology, Celltex Therapeutics enables stem cells to be used for regenerative therapy for conditions like vascular, autoimmune and degenerative diseases.

Founded: 2006

Focus: Cell Therapy

What they do: InGeneron is a clinical stage cell therapy company that specializes in novel, evidence-based regenerative medicine therapies. The companys therapy is designed to repair injured tissue, improve the quality of life for patients and modify the progression of their disease. InGeneron focuses mainly on musculoskeletal indications such as pain management.

Founded: 2006

Focus: Cancer Treatment

What they do: Moleculin Biotech is a pharmaceutical company dedicated to the treatment of highly resistant cancers and viruses. The company develops oncology drug candidates for highly resistant tumors as well as as prodrug to exploit the potential uses of inhibitors of glycolysis. Guided by the aim to provide new hope to cancer patients, Moleculin Biotech focuses on discovering new treatments for acute myeloid leukemia, skin cancer, pancreatic cancer and brain tumors.

Founded: 2001

Focus: Nanomedicine

What they do: Nanospectra Biosciences is spearheading a patient-centric use of nanomedicine for the removal of cancerous tissues. The companys ultra-focal nanoshell technology is designed to thermally destroy solid tumors without damaging adjacent healthy tissue. Nanospectra Biosciences aims to maximize treatment efficacy while minimizing side effects associated with surgery, radiation and traditional focal therapies.

Founded: 2018

Focus: Cell Therapy

What they do: Marker Therapeutics is an immuno-oncology company that focuses on the development of next-generation T cell-based immunotherapies. With the aim of treating hematological malignancies and solid tumor indications, the company uses its own MultiTAA T cell technology, which is based on the selective expansion of non-engineered, tumor-specific T cells. Marker Therapeutics is also working on developing proprietary DNA expression technology that is intended to improve the cellular immune systems ability to recognize and destroy diseased cells.

Founded: 2008

Focus: 3D Cell Culture

What they do: Nano3D Biosciences is dedicated to the development of 3D cell culture solutions. The companys core technology allows them to levitate or bioprint cells, which results in the formation of cultures that are more easily assembled and handled. Nano3D Biosciences products and services are intended for biomedical research, drug discovery, precision medicine, toxicology and regenerative medicine.

Founded: 2017

Focus: Small Molecule Inhibitors

What they do: Tvardi Therapeutics is a clinical-stage biotech company working on a new class of medicines for cancer, chronic inflammation and fibrosis. The company is focusing on the creation of orally delivered, small molecule inhibitors of STAT3, which is a key regulatory protein positioned at the intersection of many disease pathways. Tvardi Therapeutics is dedicated to delivering safe and effective solutions for use in the treatment of numerous diseases.

Founded: 2011

Focus: Targeted Cancer Therapies

What they do: Salarius Pharmaceuticals focuses on developing targeted therapies to treat various types of cancers. The companys lead candidate, Seclidemstat, is intended to treat Ewing sarcoma, a pediatric and young adult bone cancer that currently lacks targeted therapies. Salarius Pharmaceuticals performs clinical trials for the treatment of other advanced solid tumors including prostate, breast and ovarian cancers.

Founded: 2013

Focus: Genomic Medicine

What they do: Founded by Michael Metzker, RedVault Biosciences develops technologies with the aim of advancing genomic medicine. The company is currently working on a variety of projects including the development of sequencing technologies to determine haplotypes and structural variation in complex genomes. RedVault Biosciences is dedicated to identifying technology needs, creating and testing ideas, and transferring deliverables to production and distribution.

Founded: 2010

Focus: DNA Sequencing

What they do: Avance Biosciences focuses on assay development, assay validation and sample testing using next-generation DNA sequencing and other biological methods. The company offers biologics testing, diagnostic assay validation, GMO genomic testing, gene / cell therapy testing, digital and real-time PCR, microbial testing and more. Avance Biosciences aim is to assist its clients in advancing drug development and genomic research.

Founded: 2008

Focus: Bioremediation

What they do: Bionex Technology develops cost-effective, natural solutions for cleaning oil-polluted soil. The companys Super Microbe spill solution is naturally derived from microbes that digest and convert harmful contaminants on the ground and in soil, therefore lowering flammability, suppressing harmful vapors and creating a safer environment for spill responders. Bionex Technology offers a variety of other bioremediation products such as a customizable degreaser and detergent used for cleaning industrial tools.

Founded: 2016

Focus: Stem Cell Research

What they do: Located in nearby Sugar Land, Hope Biosciences is dedicated to developing stem cell-based therapies that are safe, effective and secure. The companys proprietary technology enables patients to make virtually unlimited and identical stem cells from their own tissue. Hope Biosciences offers stem cell banking solutions for both adults and newborns.

Founded: 2013

Focus: Interventional Cardiology

What they do: Saranas has created technology that enables the early detection and monitoring of bleeding complications associated with vascular access procedures. The companys monitoring system checks changes in the blood vessels electrical resistance before monitoring if bleeding has occurred from an unintentionally injured blood vessel. Saranas aims to allow physicians to mitigate downstream consequences by addressing bleeds before they become complications.

Founded: 1984

Focus: Microbiology

What they do: Microbiology Specialists Inc. specializes in microbiology testing, playing a role in microbial investigations and studies. The company also focuses on infectious disease diagnosis, forensic bacteriology and mycology, medical device testing and infection prevention. Microbiology Specialists Inc. is committed to delivering reliable, accurate and cost-effective microbiological results.

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15 Biotech Companies In Houston To Know - Built In

With a full devotion and dedication this superior GLOBAL HUMAN EMBRYONIC STEM CELL MARKET report is presented to the clients that extend their reach to success. Market parameters covered in this advertising report can be listed as market definition, currency and pricing, market segmentation, market overview, premium insights, key insights and company profile of the key market players. Each parameter included in this GLOBAL HUMAN EMBRYONIC STEM CELL MARKET business research report is again explored deeply for the better and actionable market insights. Geographical scope of the products is also carried out comprehensively for the major global areas which helps define strategies for the product distribution in those areas.

TheGlobal Human Embryonic Stem Cell Marketstudy with 100+ market data Tables, Pie Chat, Graphs & Figures is now released by Data Bridge Market Research. The report presents a complete assessment of the Market covering future trend, current growth factors, attentive opinions, facts, and industry validated market data forecast till 2026. Delivering the key insights pertaining to this industry, the report provides an in-depth analysis of the latest trends, present and future business scenario, market size and share ofMajor Players such as Arizona Board of Regents, STEMCELL Technologies Inc, Cellular Engineering Technologies, CellGenix GmbH, PromoCell GmbH, Lonza, Kite Pharma, Takeda Pharmaceutical Company Limited, BrainStorm Cell Limited., CELGENE CORPORATION, Osiris Therapeutics,Inc, U.S. Stem Cell, Inc and amny More

Global human embryonic stem cell market estimated to register a healthy CAGR of 10.5% in the forecast period of 2019 to 2026. The imminent market report contains data for historic year 2017, the base year of calculation is 2018 and the forecast period is 2019 to 2026. The growth of the market can be attributed to the increase in tissue engineering process.

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Market Dynamics:

Set of qualitative information that includes PESTEL Analysis, PORTER Five Forces Model, Value Chain Analysis and Macro Economic factors, Regulatory Framework along with Industry Background and Overview.

Global Human Embryonic Stem Cell Market By Type (Totipotent Stem Cells, Pluripotent Stem Cells, Unipotent Stem Cells), Application (Regenerative Medicine, Stem Cell Biology Research, Tissue Engineering, Toxicology Testing), End User (Research, Clinical Trials, Others), Geography (North America, Europe, Asia-Pacific, South America, Middle East and Africa) Industry Trends and Forecast to 2026

Global Human Embryonic Stem Cell Research Methodology

Data Bridge Market Research presents a detailed picture of the market by way of study, synthesis, and summation of data from multiple sources.The data thus presented is comprehensive, reliable, and the result of extensive research, both primary and secondary. The analysts have presented the various facets of the market with a particular focus on identifying the key industry influencers.

Major Drivers and Restraints of the Human Embryonic Stem Cell Industry

Complete report is available (TOC) @https://www.databridgemarketresearch.com/toc/?dbmr=global-human-embryonic-stem-cell-market

The titled segments and sub-section of the market are illuminated below:

By Type

By Application

By End User

Top Players in the Market are:

Some of the major companies functioning in global human embryonic stem cell market are Arizona Board of Regents, STEMCELL Technologies Inc, Cellular Engineering Technologies, CellGenix GmbH, PromoCell GmbH, Lonza, Kite Pharma, Takeda Pharmaceutical Company Limited, BrainStorm Cell Limited., CELGENE CORPORATION, Osiris Therapeutics,Inc, U.S. Stem Cell, Inc, Waisman Biomanufacturing, Caladrius, Pfizer Inc., Thermo Fisher Scientific, Merck KGaA, Novo Nordisk A/S, Johnson & Johnson Services, Inc and SA Biosciences Corporation among others.

How will the report help new companies to plan their investments in the Human Embryonic Stem Cell market?

The Human Embryonic Stem Cell market research report classifies the competitive spectrum of this industry in elaborate detail. The study claims that the competitive reach spans the companies of.

The report also mentions about the details such as the overall remuneration, product sales figures, pricing trends, gross margins, etc.

Information about the sales & distribution area alongside the details of the company, such as company overview, buyer portfolio, product specifications, etc., are provided in the study.

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Some of the Major Highlights of TOC covers:

Chapter 1: Methodology & Scope

Definition and forecast parameters

Methodology and forecast parameters

Data Sources

Chapter 2: Executive Summary

Business trends

Regional trends

Product trends

End-use trends

Chapter 3: Human Embryonic Stem Cell Industry Insights

Industry segmentation

Industry landscape

Vendor matrix

Technological and innovation landscape

Chapter 4: Human Embryonic Stem Cell Market, By Region

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GLOBAL HUMAN EMBRYONIC STEM CELL MARKET Analysis 2020 With COVID 19 Impact Analysis| Leading Players, Industry Updates, Future Growth, Business...

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) announced that new data from its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin gene therapy for adult and adolescent patients with sickle cell disease (SCD) show a near-complete reduction of serious vaso-occlusive crises (VOCs) and acute chest syndrome (ACS). These data are being presented at the Virtual Edition of the 25th European Hematology Association (EHA25) Annual Congress.

Vaso-occlusive crises (VOCs) are the painful, life-threatening episodes that are the primary clinical manifestation of sickle cell disease. The nearly complete elimination of VOCs that we saw in this study is impressive and demonstrates the potential of LentiGlobin for SCD as a treatment for this serious disease, said David Davidson, M.D., chief medical officer, bluebird bio. These results illustrate the type of outcomes we believe are needed to provide truly meaningful improvements for people living with sickle cell disease. In addition, the improvement of laboratory measures of hemolysis and red cell physiology, with nearly pan-cellular distribution of the anti-sickling HbAT87Q, suggest LentiGlobin for SCD may substantially modify the causative pathophysiology of SCD. We are pleased to have reached a general agreement with the FDA on the clinical data required to support a submission for LentiGlobin for SCD and we plan to seek an accelerated approval. We look forward to working with the entire SCD community to bring forward a disease modifying option for patients.

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOCs. For adults and children living with SCD, this means painful crises and other life altering or life-threatening acute complicationssuch as ACS, stroke and infections. If patients survive the acute complications, vasculopathy and end-organ damage, resulting complications can lead to pulmonary hypertension, renal failure and early death; in the U.S. the median age of death for someone with sickle cell disease is 43 - 46 years.

As a physician treating sickle cell for over 10 years, the excruciating pain crises that my patients suffer from is one of the most challenging and frustrating aspects of this disease, said presenting study author Julie Kanter, M.D., University of Alabama at Birmingham. The promising results of this study, which show patients have an almost complete elimination of VOCs and ACS, suggest LentiGlobin for SCD has real potential to provide a significant impact for people living with sickle cell disease.

LentiGlobin for SCD was designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once patients have the A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin, HbAT87Q, that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As of March 3, 2020, a total of 37 patients have been treated with LentiGlobin for SCD to-date in the HGB-205 (n=3) and HGB-206 (n=34) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2) and C (n=25).

HGB-206: Group C Updated Efficacy Results

In Group C of HGB-206, 25 patients were treated with LentiGlobin for SCD and have up to 24.8 months of follow-up (median of 12.1; min.-max.: 2.824.8 months). Results from Group C are as of March 3, 2020 and include efficacy data for 16 patients who had at least a Month 6 visit, and safety data for 18 patients, which includes two patients who were at least six months post-treatment but results from a Month 6 visit are not available.

In 16 patients with six or more months of follow-up, median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Q contributing at least 40% of total hemoglobin. At last visit reported, total hemoglobin ranged from 9.6 16.2 g/dL and HbAT87Q levels ranged from 2.7 9.4 g/dL. At Month 6 the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin. Patients had a median of 60% HbS. All patients in Group C were able to stop regular blood transfusions and remain off transfusions at three months post-treatment.

There was a 99.5% mean reduction in annualized rate of VOC and ACS among the 14 patients who had at least six months of follow-up and a history of VOCs or ACS, defined as four or more VOC or ACS events in the two years prior to treatment. These 14 patients had a median of eight events in the two years prior to treatment (min.-max.: 4 28 events).

There were no reports of serious VOCs or ACS at up to 24 months post-treatment in patients with at least six months of follow-up (n=18). As previously reported, one non-serious Grade 2 VOC was observed in a patient approximately 3.5 months post-treatment with LentiGlobin for SCD.

In sickle cell disease, red blood cells become sickled and fragile, rupturing more easily than healthy red blood cells. The breakdown of red blood cells is hemolysis and this process occurs normally in the body. However, in sickle cell disease hemolysis happens too quickly due to the fragility of the red blood cells, which results in hemolytic anemia.

Patients treated with LentiGlobin for SCD demonstrated improvement in key markers of hemolysis, which are indicators of the health of red blood cells. Lab results assessing these indicators were available for the majority of the 18 patients with 6 months of follow-up. The medians for reticulocyte counts (n=15), lactate dehydrogenase (LDH) levels (n=13) and total bilirubin (n=16) improved compared to screening and stabilized by Month 6. In patients with Month 24 data (n=5) these values approached the upper limit of normal by Month 24. These results suggest treatment with LentiGlobin for SCD is improving biological markers of sickle cell disease.

Assays were developed by bluebird bio to enable the detection of HbAT87Q and HbS protein in individual red blood cells as well as to assess if HbAT87Q was pancellular, present throughout all of a patients red blood cells. Samples from a subset of patients in Group C were assessed. In nine patients who had at least six months of follow-up, the average proportion of red blood cells positive for HbAT87Q was greater than 70%, and on average more than 85% of red blood cells contained HbAT87Q at 18 months post-treatment, suggesting near-complete pancellularity of HbAT87Q distribution.

HGB-206: Group C Safety Results

As of March 3, 2020, the safety data from all patients in HGB-206 are generally reflective of underlying SCD and the known side effects of hematopoietic stem cell collection and myeloablative conditioning. There were no serious adverse events related to LentiGlobin for SCD, and the non-serious, related adverse events (AEs) were mild-to-moderate in intensity and self-limited.

One patient with a history of frequent pre-treatment VOE, pulmonary and systemic hypertension, venous thrombosis, obesity, sleep apnea and asthma had complete resolution of VOEs following treatment, but suffered sudden death 20 months after treatment with LentiGlobin for SCD. The patients autopsy revealed cardiac enlargement and fibrosis, and concluded the cause of death was cardiovascular, with contributions from SCD and asthma. The treating physician and an independent monitoring committee agreed this death was unlikely related to LentiGlobin for SCD gene therapy.

The presentation is now available on demand on the EHA25 website:

About HGB-206

HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for SCD that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=25). A refined manufacturing process that was designed to increase vector copy number (VCN) and improve engraftment potential of gene-modified stem cells was used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

LentiGlobin for Sickle Cell Disease Regulatory Status

bluebird bio reached general agreement with the U.S. Food and Drug Administration (FDA) that the clinical data package required to support a Biologics Licensing Application (BLA) submission for LentiGlobin for SCD will be based on data from a portion of patients in the HGB-206 study Group C that have already been treated. The planned submission will be based on an analysis using complete resolution of severe vaso-occlusive events (VOEs) as the primary endpoint with at least 18 months of follow-up post-treatment with LentiGlobin for SCD. Globin response will be used as a key secondary endpoint.

bluebird bio anticipates additional guidance from the FDA regarding the commercial manufacturing process, including suspension lentiviral vector. bluebird bio announced in a May 11, 2020 press release it plans to seek an accelerated approval and expects to submit the U.S. BLA for SCD in the second half of 2021.

About LentiGlobin for Sickle Cell Disease

LentiGlobin for sickle cell disease is an investigational gene therapy being studied as a potential treatment for SCD. bluebird bios clinical development program for LentiGlobin for SCD includes the ongoing Phase 1/2 HGB-206 study and the ongoing Phase 3 HGB-210 study.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD.

The U.S. FDA granted orphan drug designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD is investigational and has not been approved in any geography.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of betibeglogene autotemcel for -thalassemia or LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders, including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using three gene therapy technologies: gene addition; cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash., Durham, N.C., and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

bluebird bio Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the companys development and regulatory plans for the LentiGlobin for SCD product candidate, and the companys intentions regarding the timing for providing further updates on the development of the product candidate. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that the COVID-19 pandemic and resulting impact on our operations and healthcare systems will affect the execution of our development plans or the conduct of our clinical studies; the risk that even if LentiGlobin for SCD addresses ACS and VOC events, that it may not address progressive organ damage experienced by patients with SCD; the risk that the efficacy and safety results observed in the patients treated in our prior and ongoing clinical trials of LentiGlobin for SCD may not persist or be durable; the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in when treating additional patients in our ongoing or planned clinical trials; the risk that the HGB-206 and HGB-210 clinical studies as currently contemplated may be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidate, resulting in a delay to our anticipated timelines for regulatory submissions, including our application for marketing approval. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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New Data Show Near Elimination of Sickle Cell Disease-Related Vaso-Occlusive Crises and Acute Chest Syndrome in Phase 1/2 Clinical Study of bluebird...

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) today announced that new data from ongoing Phase 3 studies of betibeglogene autotemcel (beti-cel; formerly LentiGlobin for -thalassemia gene therapy) show pediatric, adolescent and adult patients with a range of genotypes of transfusion-dependent -thalassemia (TDT) achieve and maintain transfusion independence with hemoglobin (Hb) levels that are near-normal (10.5 g/dL). These data are being presented at the Virtual Edition of the 25th European Hematology Association (EHA25) Annual Congress.

With more than a decade of clinical experience evaluating gene therapy in patients with transfusion dependent -thalassemia across a wide range of ages and genotypes, we have built the most comprehensive understanding of treatment outcomes in the field, said David Davidson, M.D., chief medical officer, bluebird bio. Seeing patients achieve transfusion independence and maintain that positive clinical benefit over time with robust hemoglobin levels reflects our initial vision of the potential of beti-cel. The accumulating long-term data demonstrating improvements in bone marrow histology, iron balance and red cell biology support the potential of beti-cel to correct the underlying pathophysiology of transfusion-dependent -thalassemia.

A total of 60 pediatric, adolescent and adult patients across genotypes of TDT have been treated with beti-cel in the Phase 1/2 Northstar (HGB-204) and HGB-205 studies, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies as of March 3, 2020. In studies of beti-cel, transfusion independence is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

TDT is a severe genetic disease caused by mutations in the -globin gene that results in significantly reduced or absent adult hemoglobin (HbA). In order to survive, people with TDT maintain Hb levels through lifelong, chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Patients with transfusion-dependent -thalassemia do not make enough healthy red blood cells and cannot live without chronic transfusions; for patients that means a lifetime of necessary visits to a hospital or clinic and reliance on an often unreliable blood supply, which compounds the challenges of managing this disease, said presenting study author Professor John B. Porter, MA, M.D., FRCP, FRCPath, University College London Hospital, London, UK. These results showing patients free from transfusions and maintaining near-normal hemoglobin levels after treatment with beti-cel is a positive outcome for people living with transfusion-dependent -thalassemia. In addition, we now have more data that provide further evidence that most of these patients have a measurable improvement in markers of healthy red blood cell production.

Beti-cel is a one-time gene therapy designed to address the underlying genetic cause of TDT by adding functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). This means there is no need for donor HSCs from another person, as is required for allogeneic HSC transplantation (allo-HSCT). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived Hb, at levels that eliminate or significantly reduce the need for transfusions.

Northstar-2 (HGB-207) Efficacy

As of March 3, 2020, all 23 patients in HGB-207 were treated and have been followed for a median of 19.4 months. These patients ranged in age from four to 34 years, including eight pediatric (<12 years of age) and 15 adolescent/adult (>12 years of age) patients. Only 19 patients were evaluable for transfusion independence; four additional patients do not yet have sufficient follow-up to be assessed for transfusion independence.

Eighty-nine percent of evaluable patients (17/19) achieved transfusion independence, with median weighted average total Hb levels of 11.9 g/dL (min-max: 9.4 12.9 g/dL) over a median of 19.4 months of follow-up to date (min-max: 12.3 31.4 months). These 17 patients previously required a median of 17.5 transfusions per year (min-max: 11.5 37 transfusions per year).

Improved iron levels, as measured by serum ferritin and hepcidin levels (proteins involved in iron storage and homeostasis), were observed and trends toward improved iron management were seen. Over half of patients stopped chelation therapy, which is needed to reduce excess iron caused by chronic blood transfusions. Seven out of 23 patients began using phlebotomy for iron reduction.

Analysis of Healthy Red Blood Cell Production

In exploratory analyses, biomarkers of ineffective erythropoiesis (red blood cell production) were evaluated in patients who achieved transfusion independence in HGB-207.

The myeloid to erythroid (M:E) ratio in bone marrow from patients who achieved transfusion independence increased from a median of 1:3 (n=17) at baseline to 1:1.2 (n=16) at Month 12. Improvement of the M:E ratio, the ratio of white blood cell and red blood cell precursors in the bone marrow, suggests an improvement in mature red blood cell production. Images illustrating the bone marrow cellularity at baseline, Month 12 and Month 24 are available in the EHA25 presentation (abstract #S296): Improvement in erythropoiesis in patients with transfusion-dependent -thalassemia following treatment with betibeglogene autotemcel (LentiGlobin for -thalassemia) in the Phase 3 HGB-207 study.

Additionally, biomarkers of erythropoiesis continue to demonstrate a trend toward normalization in patients who achieved transfusion independence, including improved levels over time of erythropoietin, a hormone involved in red blood cell production; reticulocytes, immature red blood cells; and soluble transferrin receptor, a protein measured to help evaluate iron status. The continued normalization of red blood cell production over time among some patients who achieved transfusion independence supports the disease-modifying potential of beti-cel in patients with TDT.

Northstar-3 (HGB-212) Efficacy

As of March 3, 2020, 15 patients (genotypes: 9 0/0, 3 0/ +IVS1-110, 3 homozygous IVS-1-110 mutation) were treated and had a median follow-up of 14.4 months (min-max: 1.124.0 months). Median age at enrollment was 15 (min-max: 4 33 years).

Six of eight evaluable patients achieved transfusion independence, with median weighted average total Hb levels of 11.5 g/dL (min-max: 9.5 13.5 g/dL), and continued to maintain transfusion independence for a median duration of 13.6 months (min-max: 12.2 21.2 months) as of the data cutoff.

Eighty-five percent of patients (11/13) with at least seven months of follow-up had not received a transfusion in more than seven months at time of data cutoff. These 11 patients previously required a median of 18.5 transfusions per year (min-max: 11.0 39.5 transfusions per year). In these patients, gene therapy-derived HbAT87Q supported total Hb levels ranging from 8.814.0 g/dL at last visit.

Betibeglogene autotemcel Safety

Non-serious adverse events (AEs) observed during the HGB-207 and HGB-212 trials that were considered related or possibly related to beti-cel were tachycardia, abdominal pain, pain in extremities, leukopenia, neutropenia and thrombocytopenia. One serious event of thrombocytopenia was considered possibly related to beti-cel.

In HGB-207, serious events post-infusion in two patients included three events of veno-occlusive liver disease and two events of thrombocytopenia. In HGB-212, serious events post-infusion in two patients included two events of pyrexia.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

In both Phase 3 studies, there have been no deaths, no graft failure, no cases of vector-mediated replication competent lentivirus or clonal dominance, no leukemia and no lymphoma.

The presentations are now available on demand on the EHA25 website:

About betibeglogene autotemcel

The European Commission granted conditional marketing authorization (CMA) for betibeglogene autotemcel (beti-cel; formerly LentiGlobin gene therapy for -thalassemia), marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent -thalassemia (TDT) who do not have a 0/0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for ZYNTEGLO, supported by data from 32 patients treated with ZYNTEGLO, including three patients with up to five years of follow-up.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Beti-cel adds functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity and non-cardiac chest pain. Two serious adverse events (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

The CMA for beti-cel is valid in the 27 member states of the EU as well as UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration (FDA) granted beti-cel orphan drug designation and Breakthrough Therapy designation for the treatment of transfusion-dependent -thalassemia. Beti-cel is not approved in the U.S.

Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit http://www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207) and NCT03207009 for Northstar-3 (HGB-212).

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of betibeglogene autotemcel or LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of bluebird bio, Inc.

bluebird bio Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that the COVID-19 pandemic and resulting impact on our operations and healthcare systems will affect the execution of our development plans or the conduct of our clinical studies; the risk that the efficacy and safety results observed in the patients treated in our prior and ongoing clinical trials of beti-cel may not persist; and the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated with additional patients in our ongoing or planned clinical trials or in the commercial context; the risk that the FDA will require additional information regarding beti-cel, resulting in a delay to our anticipated timelines for regulatory submissions, including submission of our BLA. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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Majority of Evaluable Patients Across Genotypes Achieve Transfusion Independence and Maintain It with Near-Normal Hemoglobin Levels in Phase 3 Studies...

The company said the move was aimed at the development of next generation cellular immunotherapy FLASH-CAR technology

(), a clinical-stage developer of cell-based technologies and therapeutics, announced Thursday that it has struck a three-way material transfer agreement (MTA) with Weill Cornell Medicine in New York City and the companys strategic partner, Arbele Limited.

With this agreement, Avalon GloboCare and Arbele Limited intend to collaborate with Weill Cornell Medicine and co-develop the standardized laboratory steps necessary to generate clinical-grade CAR-T and CAR-natural killer (NK) cells for use in future human clinical trials with Avalons first FLASH-CAR platform candidate, AVA-011.Similar to T-cells, NK cells are a type of white blood cell, also able to attack cancer cells, but utilize different mechanisms.

The company said this process development step will provide the bridge between Avalons benchtop research and the bio-manufacturing processes to potentially deliver the clinical-grade cellular immunotherapy product to patients.

READ:Avalon GloboCare advancing immune cell therapy to treat blood cancers using FLASH-CAR technology

We are excited about this agreement to translate our cellular therapy candidates into standardized, clinical-grade cell products that could be used in future clinical trials, Avalon GloboCare CEO David Jin said in a statement.

This step reflects our dedication to establishing an infrastructure to develop our cellular immunotherapy candidates and to maintain the highest possible standards for generating clinical-grade cells for human cancer trials, he added.

AVA-011 is a next generation cellular immunotherapy candidate using Avalons FLASH-CAR technology that targets both CD19 and CD22 tumor antigens on cancer cells. Avalon has already successfully completed pre-clinical research on AVA-011, including tumor cytotoxicity studies.

Avalon expects to begin a first-in-human clinical trial with AVA-011 for the treatment of relapsed or refractory B-cell lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma in the first quarter of 2021. The goal is to use AVA-011 as a bridge to bone marrow stem cell transplant therapy, currently the only curative approach for patients with these blood cancers.

Avalons next generation immune cell therapy using FLASH-CAR technology is being co-developed with the companys strategic partner Arbele Limited. The adaptable FLASH-CAR platform can be used to create personalized cell therapy from a patients own cells, as well as off-the-shelf cell therapy from a universal donor, expanding the reach of cancer patients that can be treated.

Avalon, based in Freehold, New Jersey, specializes in developing cell-based technologies and is involved in the management of stem-cell banks and clinical laboratories.

Contact the author Uttara Choudhury at [emailprotected]

Follow her on Twitter: @UttaraProactive

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Avalon GloboCare strikes three-way material transfer agreement with Weill Cornell Medicine and Arbele Limited - Proactive Investors USA & Canada

Professor Michael P Lisanti, Chair in Translational Medicine at the University of Salford, has been an active research scientist for more than 30 years and is an expert in the field of cellular senescence. In 2018 Lisanti, along with his wife and research partner Professor Federica Sotgia, co-authored a paper entitled Azithromycin and Roxithromycin define a new family of senolytic drugs that target senescent human fibroblasts, which identified the FDA-approved antibiotic azithromycin as a senolytic drug: a compound which can be used to treat the symptoms of ageing.

Their research was made possible through generous funding contributions from Lunella Biotech, Inc, a Canadian-based pharmaceutical developer which fosters medical innovation; the Foxpoint Foundation, also based in Canada; and the Healthy Life Foundation, a UK charity which funds research into ageing and age-related conditions. Lisanti speaks to HEQ about his work and the future of senescence studies.

We started out focusing on cancer, but the relationship between cancer and ageing led us to shift our focus towards senescence, the process by which cells chronologically age and go into cell cycle arrest. Senescence leads to chronic inflammation: the cells secrete a lot of inflammatory mediators, which allows the cells to become almost infectious; so then neighbouring normal cells become senescent it has a kind of cataclysmic effect. As you age especially as you approach around 50 you begin to accumulate more senescent cells, which are thought to be the root cause of ageing; this then leads to various ageing-associated diseases, such as heart disease, diabetes, dementia and cancer, the most life threatening conditions in the Western world.

The goal, therefore, would be to remove the senescent cells. It is possible to use a genetic trick to remove senescent cells from mice: this causes them to live longer by preventing ageing-associated diseases; but it is not possible to use the same genetic trick for humans. We would therefore need a drug that only kills or removes senescent cells; and that could then potentially lead to rejuvenation, thereby extending the patients healthy lifespan.

We set up a drug assay using normal, commercially available, human fibroblasts: MRC-5, which comes from the lungs, and BJ-1, which comes from the skin. The idea was to artificially induce ageing, which we did using a compound called BrdU. This compound is a nucleoside: it incorporates into the DNA and that leads to DNA damage; and the DNA damage in turn induces the senescence phenotype. The overarching concept was to create a population of cells artificially that were senescent; and then to compare primary cells that were normal with cells which were senescent, with the goal of identifying drugs which could only selectively kill the senescent cells and not harm the normal cells.

We had previously observed positive results in tests on the metabolic effects of antibiotics, so our drug screening identified two drugs called azithromycin and roxithromycin, which constitute a new family of senolytic drugs. Theyre both clinically approved drugs azithromycin has been around longer; and has a strong safety profile and we looked at other members of the same drug family such as erythromycin, which is the parent compound, but erythromycin has no senolytic activity. The characteristics we were looking for appeared to be relatively restricted to azithromycin, which in our observation was very efficiently killing the senescent cells. As we reported in the paper, it had an efficacy of approximately 97%, meaning that it was able to facilitate the growth of the normal cells, while concurrently selectively killing the senescent cells.

We tested the drug on normal and senescent cells which were otherwise identical. The senescent cells underwent apoptosis programmed cell death so that led us to the conclusion that the drug selectively kills the senescent cells, while at the same time the normal cells are able to continue to proliferate. That selective effect of removing exclusively the senescent cells is what we were searching for; because in this instance we would want a drug that could potentially be used in humans and which would only kill senescent cells.

Obviously, we would have to do clinical trials going forward, but the first step should be to identify the pharmaceutical application. Given that this drug appears to selectively kill and remove the senescent cells, it could be used potentially to prevent ageing-associated disease; and it could therefore potentially extend the human lifespan, especially in terms of reducing diseases and conditions like diabetes, heart disease, dementia and even cancer.

Cystic fibrosis is the most common genetic disease in humans; patients with cystic fibrosis are prone to bacterial lung infections. Researchers started to explore the possibility of using azithromycin preventatively in patients with cystic fibrosis; and they found that, while it didnt necessarily affect patients susceptibility to infection, it did prevent lung fibrosis where the lungs become stiff and the patient is unable to breathe and in doing so, extended the patients lifespan. These studies were focused on myofibroblasts, which at the time werent really seen as senescent; whereas the literature now acknowledges a general consensus that myofibroblasts are indeed senescent cells.

We havent specifically examined anything relating ageing to antimicrobial resistance; but azithromycin is an antibiotic, which is not ideal within the context of AMR. Potentially in the future, once researchers identify what it is about the azithromycin that is causing the senescent cells to die, they could develop future drugs azithromycin is a stepping stone in this context, but what it shows is proof of principle that a drug can be identified which selectively kills senescent cells. This indicates that senescent cells are clearly biochemically distinct from the normal cells, and that it is possible to find a drug that selectively kills them and that is relatively safe. It provides a starting point for further new drug discovery to identify other drugs which might also be selective.

Ideally, we would want a drug which is not an antibiotic; but that means further research will be necessary to find additional drugs or to refine the senolytic activity which weve discovered in this drug. We are in the early stages; the point is that it is experimentally feasible and this would then lend itself to doing new clinical trials in the future, because azithromycin is relatively safe and it probably wont need to be administered over a long period of time to remove senescent cells you might not need to use it for any longer than you would as an antibiotic.

This research has been supported by the Foxpoint Foundation (Canada), the Healthy Life Foundation (UK), and Lunella Biotech, Inc. (Canada).

Professor Michael P Lisanti is Chair of Translational Medicine at the University of Salford School of Science, Engineering & Environment, UK. His current research programme is focused on eradicating cancer stem cells (CSCs); and anti-ageing therapies, in the context of age-associated diseases, such as cancer and dementia.

Lisanti began his education at New York University, US, graduating magna cum laude in chemistry (1985); before completing an MD-PhD in cell biology and genetics at Cornell University Medical College, US (1992). In 1992, he moved to MIT, US, where he worked alongside Nobel laureate David Baltimore and renowned cell biologist Harvey Lodish as a Whitehead Institute fellow (1992-96).

His career has since taken him to the Albert Einstein College of Medicine, US (1997-2006), the Kimmel Cancer Center, US (2006-12), and the University of Manchester, UK (2012-16), where he served as the Muriel Edith Rickman chair of breast oncology, director of the Breakthrough Breast Cancer and the Breast Cancer Now Research Units, and founder and director of the Manchester Centre for Cellular Metabolism.

Lisanti has contributed to 564 publications in peer-reviewed journals and been cited more than 90,000 times. A list of his works can be found at: https://pubmed.ncbi.nlm.nih.gov/?term=lisanti+mp&sort=date

Professor Federica Sotgia currently serves as chair in cancer biology and ageing at the University of Salford School of Science, Engineering and Environment, UK, where she focuses on, inter alia, the role of the tumour microenvironment in cancer and the metabolic requirements of tumour-initiating cells.

Sotgia graduated magna cum laude with an MS in biological sciences (1996) from the University of Genova, Italy, where she later completed a PhD in medical genetics (2001). She moved to the Albert Einstein College of Medicine, US, in 1998, originally as a visiting student and then postdoctoral fellow, and she was appointed an instructor in 2002.

Sotgia has since worked as an assistant professor at the Kimmel Cancer Center, US (2006-12), a senior lecturer at the University of Manchester, UK (2012-16), and a Professor in biomedical science at the University of Salford (2016-present).

She has contributed to 206 publications in peer-reviewed journals and been cited upwards of 27,000 times.

A list of her works can be found at: https://pubmed.ncbi.nlm.nih.gov/?term=sotgia+f&sort=date

Professor Michael P Lisanti, MD-PhD, FRSA, FRSBChair in Translational MedicineSchool of Science, Engineering & EnvironmentUniversity of Salford+44 (0)1612 950 240M.P.Lisanti@salford.ac.uk

This article is from issue 13 of Health Europa. Clickhere to get your free subscription today.

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Senolytic drugs: can this antibiotic treat symptoms of ageing? - Health Europa

(MENAFN - GetNews) Market Research Future (MRFR) collected data on several factors including implications of COVID 19 Impact on Regenerative Medicine Market and demographic challenges, showed how it could move forward in the coming years.

Regenerative Medicine Market Outlook

Global regenerative medicine market is growing continually, witnessing a massive uptake. Market growth primarily attributes to the increasing advancement in healthcare technology and the growing prevalence of chronic diseases. Besides, improvements in the field of regenerative medicine and stem cell technology drive the growth of the market excellently.

Moreover, the rising uptake of therapeutics such as stem cell biology, cellular therapy, tissue engineering in applications, including cord blood, oncology, urology, orthopedics, neurology, dermatology, and others accelerate the market growth. According to Market Research Future (MRFR), the global regenerative medicine market is poised to grow at 25.4% CAGR throughout the forecast period (2016 2022).

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Additionally, the rising uptake of stem cell & tissue engineering processes in the treatment of health issues ranging from orthopedics, musculoskeletal & spine, dental, and skin/integumentary to cancer, neurology, and cardiology substantiate the market growth. Furthermore, the increasing rate of road accidents, injuries, and trauma cases drive the market exponentially, driving the demand for transplants & surgical reconstruction procedures.

On the other hand, factors such as the lack of awareness, skilled professionals, and stringent regulatory policies are projected to act as significant impeders for market growth. Nevertheless, funding support for the development of regenerative medicines would support the growth of the market throughout the predicted period. Also, widening application areas of regenerative medicines in the field of stem cell reconstructive and skin grafting would increase the market growth.

Global Regenerative Medicine Market Segments

The analysis is segmented into four dynamics;

By Material : Synthetic Materials, Genetically Engineered Materials, Pharmaceuticals, and others.

By Therapy : Stem Cell Biology, Cellular Therapy, Tissue Engineering, and others.

By Application : Cord Blood, Oncology, Urology, Orthopedics, Neurology, Dermatology, and others.

By Regions : Americas, Europe, Asia Pacific, Middle East & Africa, and Rest-of-the-World.

Regenerative Medicine Market Regional Analysis

North America is projected to continue dominating the global regenerative medicine market throughout the forecast period. In 2015, North America accounted for more than 44% of the overall market share. This huge market growth attributes to the presence of a large number of major players and pharma & biotechnology companies. Moreover, huge investments made by public & private organizations drive the regenerative medicine industry in the region.

Besides, the rising prevalence of chronic diseases and orthopedic issues and increasing clinical trials to evaluate the therapeutic potential of products foster regional market growth. Also, the well-spread awareness towards the therapeutic potency of regenerative medicines impacts the market growth positively. The North American regenerative medicine market is expected to grow at a robust CAGR of 22.3% over the review period.

Europe stands second in the global regenerative medicine market. Factors such as the increasing per capita healthcare expenses and penetration of healthcare sectors in the region boost the market growth. Additionally, the rising government support and R & D funding in the life science developments substantiate the regional market growth. Markets in the UK, Germany, and France, contribute to the regional market majorly. The European regenerative medicine market is estimated to grow at 22.5% CAGR during the assessment period.

The Asia Pacific regenerative medicine market has emerged as a rapidly growing market. Factors such as the large advances in biotechnology and increasing government support for R & D are fostering the growth of the regional market. Regenerative medicine markets in highly populated countries such as China, India, and Japan support the regional market growth excellently, heading with huge technological advances. The APAC Regenerative Medicine market is predicted to demonstrate huge growth potential.

Global Regenerative Medicine Market - Competitive Analysis

The well-established regenerative medicine market appears to be highly competitive with the presence of several notable players. To gain a larger competitive advantage, market players incorporate strategic initiatives such as mergers & acquisitions, expansions, and product/technology launch. Also, they make substantial investments to drive R & D to develop their capabilities and to expand their global footprints. Simultaneously, R & D funding programs initiated by the governments to enhance regenerative medicine capabilities are offering high growth potential. This is further going to attract several new entrants to the market and intensify the market competition further.

Regenerative Medicine Market Major Players:

Players active in the global regenerative medicine market include Osiris Therapeutics, Cook Biotech, Organogenesis, Baxter International, Inc., Stryker and RTI surgical, LifeSciences, CryoLife, Advanced Cell Technology, Sanofi, BioMimetic Therapeutics, Medtronic, StemCellsInc, and LifeCell Kinetic Concepts, among others.

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Regenerative Medicine Industry/Innovations/Related News:

March 15, 2020 - Research team at the University of Sheffield published their study on stem cell mutations that could improve regenerative medicine in the magazine Stem Cell Reports.' Their study gives new insights into the cause of mutations in pluripotent stem cells and potential ways of stopping these mutations from occurring. It also suggests ways to reduce the likelihood of variations occurring in these cells when cultured.There is considerable interest in using Pluripotent stem cells to produce cells that can replace diseased or damaged tissues in applications referred to as regenerative medicine.

Pharmaceutical Industry Related Reports

Global Anti-viral drugs Market Information, by application (hepatitis, HIV/AIDS, herpes, influenza and others) and by mechanism of action (nucleotide polymerase inhibitors, reverse transcriptase inhibitors, protease inhibitors and others) - Forecast to 2022: https://www.marketresearchfuture.com/reports/anti-viral-drugs-market-2454

Drug allergy market information: by type (immunologic, nonimmunologic, and others), diagnosis (skin tests, blood tests, and others), by treatment (antihistamines, corticosteroids, and others), by end user- global forecast till 2023: https://www.marketresearchfuture.com/reports/drug-allergy-market-4033

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Impacts of COVID 19 on the Global Regenerative Medicine Market Size: Global Industry Analysis, Growth, Top Companies Revenue, MRFR Reveals Insights...

ORLANDO, Fla.--(BUSINESS WIRE)--Hesperos Inc., pioneers of the Human-on-a-Chip in vitro system, today announced the publication of a new peer-reviewed publication that describes how the companys technology can be used to investigate immune responses following treatment with biological therapeutics for multi-organ systemic diseases, including cancer, infectious diseases and inflammatory disorders. The study was part of a collaboration between Hesperos, Hoffman-La Roche Pharmaceuticals and the University of Central Florida. The manuscript, titled Differential Monocyte Actuation in a Three-Organ Functional Innate Immune System-on-a-Chip, was published today in the prestigious journal Advanced Science. Click here to view a multimedia version of the press release, including media-ready images, downloadable resources, and more.

The immune system plays an important role in coordinating with other organ systems to combat infection, eliminate damaged cells and repair tissue. However, modeling immune response following drug treatment in preclinical studies is challenging due to poor predictability, especially for the innate portion of the system. As the scientific community begins to turn more towards using multi-organ, human-on-a-chip systems as a cost-effective way to increase efficiency and lower toxicity, many of these models lack a systemic immune component.

Hesperos, in collaboration with Hoffmann-La Roche Pharmaceuticals, describe an in vitro, pumpless, three-organ system containing functional human cardiomyocytes, skeletal muscle and hepatocytes in a serum-free medium, along with recirculating human monocyte THP-1 immune cells. Monocytes are a vital immune system cells involved in wound healing, pathogen clearance and activation of the innate immune response, but are also responsible for the cytokine storm found in conditions such as sepsis.

One application where the immune-system-on-a-chip can be immediately useful is for uncovering how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly affects multi-organ systems by activating the cytokine storm from inflammatory macrophages and to support the rapid development of therapeutics. As the global pandemic of COVID-19 continues to grow, this system has the potential to quickly evaluate antiviral and repurposed drugs to help combat this devastating disease, said Michael L. Shuler, Ph.D., Chief Executive Officer of Hesperos.

In the study, the researchers evaluated two different innate immune responses: 1) targeted immune response following tissue-specific damage, which simulates indirect activation of THP-1 cells and, 2) pro-inflammatory immune response following direct activation of immune cells, mimicking acute inflammation and the cytokine storm. Though not reported in this study, Hesperos has also shown that peripheral blood mononuclear cells (PBMCs) and T-cells are sustainable in these multi-organs systems, which would allow some aspects of adaptive immunity to also be modeled.

In the targeted immune response experiments, the cardiotoxic compound amiodarone was used to selectively damage cardiac cells to evaluate how THP-1 immune cells affect the three-organ system. The presence of both amiodarone and THP-1 immune cells led to a more pronounced reduction in cardiac force, conduction velocity and beat frequency compared to amiodarone alone. THP-1 cells were also found to infiltrate the damaged cardiomyocytes and induce significantly increased cytokine IL-6 expression, indicating an M2 macrophage phenotype. No immune-activated damage was reported in the skeletal muscle or liver cells.

The most striking features of our immune-system-on-a-chip is that it emulates different immune reactions for direct tissue-damage and acute inflammation, as well as distinguishes between M1 vs. M2 macrophage phenotypes, said James Hickman, Ph.D., Chief Scientist at Hesperos and Professor at the University of Central Florida.

The study was initially funded by Roche Pharmaceuticals and completed under an NIH grant from National Center for Advancing Translational Sciences (NCATS) Small Business Innovation Research program, which supports studies to advance tissue chip technology toward commercialization.

Tissue chips are a promising technology for accelerating the preclinical timeline and getting treatments to patients more efficiently, said Danilo A. Tagle, Ph.D., associate director for special initiatives at NCATS. Finding improved ways to study immune responses has tremendous implications for drug discovery and the development of more effective personalized medicines in diseases that affect multiple organ systems.

In the pro-inflammatory response experiments, the three-organ system was exposed to lipopolysaccharide (LPS) and interferon gamma (IFN-) to stimulate acute inflammation/cytokine storm and provoke monocyte differentiation and activation. In the absence of THP-1 immune cells, LPS/IFN- treatment had no significant effect on function of the three-organ system. However, with the addition of THP-1 immune cells, LPS/IFN- treatment caused cellular damage to all three-organ components, including THP-1 cell infiltration in liver tissue, and led to significant alterations in cardiac force and beat frequency, as well as skeletal muscle force. Additionally, there was an upregulation of pro-inflammatory cytokines, including TNF-, IL-6 and IL-10, indicating an M1 macrophage phenotype, which is analogous to the cytokine storm found during certain reactions to biologic therapeutics and emulates what occurs during sepsis.

To read the full manuscript, please visit https://doi.org/10.1002/advs.202000323.

About Hesperos

Hesperos, Inc. is a leader in efforts to characterize an individuals biology with Human-on-a-Chip microfluidic systems. Founders Michael L. Shuler and James J. Hickman have been at the forefront of every major scientific discovery in this realm, from individual organ-on-a-chip constructs to fully functional, interconnected multi-organ systems. With a mission to revolutionize toxicology testing as well as efficacy evaluation for drug discovery, the company has created pumpless platforms with serum-free cellular mediums that allow multi-organ system communication and integrated computational PKPD modeling of live physiological responses utilizing functional readouts from neurons, cardiac, muscle, barrier tissues and neuromuscular junctions as well as responses from liver, pancreas and barrier tissues. Created from human stem cells, the fully human systems are the first in vitro solutions that accurately utilize these platforms to predict in vivo functions without the use of animal models, as featured in Science. More information is available at https://hesperosinc.com

Hesperos and Human-on-a-Chip are trademarks of Hesperos Inc. All other brands may be trademarks of their respective holders.

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Hesperos demonstrates innovative Human-on-a-Chip approach to modeling innate immune system response following tissue damage and acute inflammation -...

Stem Cell Assay Market: Snapshot

Stem cell assay refers to the procedure of measuring the potency of antineoplastic drugs, on the basis of their capability of retarding the growth of human tumor cells. The assay consists of qualitative or quantitative analysis or testing of affected tissues andtumors, wherein their toxicity, impurity, and other aspects are studied.

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With the growing number of successfulstem cell therapytreatment cases, the global market for stem cell assays will gain substantial momentum. A number of research and development projects are lending a hand to the growth of the market. For instance, the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM) has attempted to manipulate stem cells to heal eye, kidney, and heart injuries. A number of diseases such as Alzheimers, spinal cord injury, Parkinsons, diabetes, stroke, retinal disease, cancer, rheumatoid arthritis, and neurological diseases can be successfully treated via stem cell therapy. Therefore, stem cell assays will exhibit growing demand.

Another key development in the stem cell assay market is the development of innovative stem cell therapies. In April 2017, for instance, the first participant in an innovative clinical trial at the University of Wisconsin School of Medicine and Public Health was successfully treated with stem cell therapy. CardiAMP, the investigational therapy, has been designed to direct a large dose of the patients own bone-marrow cells to the point of cardiac injury, stimulating the natural healing response of the body.

Newer areas of application in medicine are being explored constantly. Consequently, stem cell assays are likely to play a key role in the formulation of treatments of a number of diseases.

Global Stem Cell Assay Market: Overview

The increasing investment in research and development of novel therapeutics owing to the rising incidence of chronic diseases has led to immense growth in the global stem cell assay market. In the next couple of years, the market is expected to spawn into a multi-billion dollar industry as healthcare sector and governments around the world increase their research spending.

The report analyzes the prevalent opportunities for the markets growth and those that companies should capitalize in the near future to strengthen their position in the market. It presents insights into the growth drivers and lists down the major restraints. Additionally, the report gauges the effect of Porters five forces on the overall stem cell assay market.

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Global Stem Cell Assay Market: Key Market Segments

For the purpose of the study, the report segments the global stem cell assay market based on various parameters. For instance, in terms of assay type, the market can be segmented into isolation and purification, viability, cell identification, differentiation, proliferation, apoptosis, and function. By kit, the market can be bifurcated into human embryonic stem cell kits and adult stem cell kits. Based on instruments, flow cytometer, cell imaging systems, automated cell counter, and micro electrode arrays could be the key market segments.

In terms of application, the market can be segmented into drug discovery and development, clinical research, and regenerative medicine and therapy. The growth witnessed across the aforementioned application segments will be influenced by the increasing incidence of chronic ailments which will translate into the rising demand for regenerative medicines. Finally, based on end users, research institutes and industry research constitute the key market segments.

The report includes a detailed assessment of the various factors influencing the markets expansion across its key segments. The ones holding the most lucrative prospects are analyzed, and the factors restraining its trajectory across key segments are also discussed at length.

Global Stem Cell Assay Market: Regional Analysis

Regionally, the market is expected to witness heightened demand in the developed countries across Europe and North America. The increasing incidence of chronic ailments and the subsequently expanding patient population are the chief drivers of the stem cell assay market in North America. Besides this, the market is also expected to witness lucrative opportunities in Asia Pacific and Rest of the World.

Global Stem Cell Assay Market: Vendor Landscape

A major inclusion in the report is the detailed assessment of the markets vendor landscape. For the purpose of the study the report therefore profiles some of the leading players having influence on the overall market dynamics. It also conducts SWOT analysis to study the strengths and weaknesses of the companies profiled and identify threats and opportunities that these enterprises are forecast to witness over the course of the reports forecast period.

Some of the most prominent enterprises operating in the global stem cell assay market are Bio-Rad Laboratories, Inc (U.S.), Thermo Fisher Scientific Inc. (U.S.), GE Healthcare (U.K.), Hemogenix Inc. (U.S.), Promega Corporation (U.S.), Bio-Techne Corporation (U.S.), Merck KGaA (Germany), STEMCELL Technologies Inc. (CA), Cell Biolabs, Inc. (U.S.), and Cellular Dynamics International, Inc. (U.S.).

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TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

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Stem Cell Assay Market to Witness Growth Acceleration During 2017-2025 - Cole of Duty

The art (and existing science) of regenerative medicine in equine practice, and whats to come

Regenerative therapy is an umbrellaterm encompassing any method that encourages the body to self- heal. Because it is drawing onits own properties, healing tissue more closely resembles native tissue than weak, disorganized scar tissue typically seen post-injury.

The goal is to allow restoration of normal function and structure of the injured tissue to allow horses to perform at their previous level, whatever that might be, with a reduced risk of reinjury, says Kyla Ortved, DVM, PhD, Dipl. ACVS, ACVSMR, assistant professor of large animal surgery at the University of Pennsylvanias New Bolton Center, in Kennett Square.

She says the three main components of regenerative medicine that help tissues self-heal include:

A specific therapy may incorporate some or all three of these components, says Ortved.

Due to the regenerative therapy industrys popularity and continued growth, many articles weve published review recent laboratory studies about stem cell production and data on efficacy andsafety (you can find them at TheHorse.com/topics/regenerative-medicine). Here, well review the basics of three regenerative modalities commonly used in equine medicine and when veterinarians and horse owners might consider each.

With this approach the practitioner collects blood from a horse and processes it using a commercial system that concentrates the platelets. When he or she injects that concentrated platelet product back into the horse, granules within the platelets release an array of growth factors that aim to facilitate and modulate the healing process. Specifically, granule-derived growth factors encourage target tissue cells at the injury site to migrate and proliferate, improve extracellular matrix synthesis, and stimulate blood vessel development.

Recently, leukocyte-reduced PRP hasbecome many equine veterinarians PRP product of choice. These preparations contain fewer white blood cells (leukocytes) and, reportedly, inflammatory mediators than normal PRP products do. These mediators break tissues down, effectively counteracting the anabolic (tissue-building) effects of the platelets and their granules.

Veterinarians can easily prepare ACS by collecting a blood sample from the patient, then incubating it with special commercially available glass beads to stimulate interleukin-1 receptor antago- nist protein (IRAP) production. Theythen inject the resultant IRAP-rich serumsample back into the patient at the target location or injury site. This protein blocks the action of interleukin-1, a powerful and damaging pro-inflammatory mediator. Additionally, glass bead incubation stimulates the production of anti-inflammatory mediators and growth factors similar to those found in PRP.

Ortved says its important to remember that all biologics, including PRP and IRAP, contain various concentrations of growth factors and bioactive protein.

Remember, they are made from your horses blood and, therefore, containall of the components in blood, just in varying concentrations, she says.

Regenerative therapies that contain highconcentrations of IRAP include IRAP II, autologous protein solution (APS), and bone marrow aspirate concentrate (BMAC).

In certain tissues, such as adipose (fat) and bone marrow, we can find specific cells that have the ability to self-renew and grow more than 200 types of body cells. Veterinarians can isolate these cells, called stem cells or progenitor cells, and either:

Perhaps more important than theirability to differentiate into other celltypes, stem cells have powerful anti-inflammatoryproperties and play acentral role in coordinating healing in alltypes of tissues through cell-to-cell signaling,Ortved says.

Which of these three modality typeswill provide the most benefit to yourhorse depends on a variety of factors thatyou and your veterinarian will consider.

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Regenerative Therapies: Helping Horses Self-Heal The Horse - TheHorse.com

KENILWORTH, N.J. & WOODCLIFF LAKE, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced new data from analyses of two trials evaluating KEYTRUDA, Mercks anti-PD-1 therapy, plus LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai. In the KEYNOTE-524/Study 116 and KEYNOTE-146/Study 111 trials, the KEYTRUDA plus LENVIMA combination demonstrated clinically meaningful objective response rates (ORR) in patients with unresectable hepatocellular carcinoma (HCC) with no prior systemic therapy and in patients with metastatic clear cell renal cell carcinoma (ccRCC) who progressed following immune checkpoint inhibitor therapy, respectively.

The tumor response rates demonstrated with KEYTRUDA plus LENVIMA in these studies underscore the potential of this combination regimen in certain types of hepatocellular and renal cell carcinoma, said Dr. Jonathan Cheng, Vice President, Oncology Clinical Research, Merck Research Laboratories. KEYTRUDA plus LENVIMA is an important pillar of our broad oncology research program, and we continue to advance the study of the combination across multiple types of cancers and stages of disease.

As data from our combination trials continue to read out, our enthusiasm for and belief in the potential of KEYTRUDA plus LENVIMA are strengthened by the growing body of evidence observed in multiple advanced cancers, said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. Our ongoing clinical study efforts on this combination exemplify our commitment to following the science and exploring possible solutions for patients affected by difficult-to-treat cancers.

Results from KEYNOTE-524/Study 116 (Abstract #4519) are being presented in a poster discussion session, and results from KEYNOTE-146/Study 111 (Abstract #5008) are being presented in an oral abstract session of the Virtual Scientific Program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

KEYNOTE-524/Study 116 Trial Design and Data (Abstract #4519)

KEYNOTE-524/Study 116 (ClinicalTrials.gov, NCT03006926) is a Phase 1b, open-label, single-arm trial evaluating the KEYTRUDA plus LENVIMA combination in 100 patients with unresectable HCC with no prior systemic therapy. Patients were treated with KEYTRUDA 200 mg intravenously every three weeks in combination with LENVIMA 8 or 12 mg (based on baseline body weight 60 kilograms or 60 kilograms, respectively) orally once daily. The primary endpoints are ORR and duration of response (DOR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1 per independent imaging review (IIR). Secondary endpoints include progression-free survival (PFS), time to progression (TTP) and overall survival (OS). At data cutoff (Oct. 31, 2019) and a median duration of follow-up of 10.6 months (95% CI: 9.2-11.5), 37 patients were still on study treatment (KEYTRUDA plus LENVIMA: n=34; LENVIMA only: n=3), and median duration of treatment exposure to the KEYTRUDA plus LENVIMA combination was 7.9 months (range: 0.2-31.1).

The final analysis of the studys primary endpoints showed the KEYTRUDA plus LENVIMA combination demonstrated an ORR of 36% (n=36) (95% CI: 26.6-46.2), with a complete response rate of 1% (n=1) and a partial response rate of 35% (n=35), and a median DOR of 12.6 months (95% CI: 6.9-not estimable [NE]), using RECIST v1.1 criteria per IIR. As assessed using mRECIST criteria per IIR, the KEYTRUDA plus LENVIMA combination demonstrated an ORR of 46% (n=46) (95% CI: 36.0-56.3), with a complete response rate of 11% (n=11) and a partial response rate of 35% (n=35), and a median DOR of 8.6 months (95% CI: 6.9-NE).

Treatment-related adverse events (TRAEs) led to discontinuation of KEYTRUDA and LENVIMA in 6% of patients, discontinuation of KEYTRUDA in 10% of patients, and discontinuation of LENVIMA in 14% of patients. Grade 3 TRAEs occurred in 67% of patients (Grade 3: 63%; Grade 4: 1%; Grade 5: 3%). There was one Grade 4 TRAE (leukopenia/neutropenia), and there were three Grade 5 treatment-related deaths (acute respiratory failure/acute respiratory distress syndrome, intestinal perforation and abnormal hepatic function; n=1 for each). The most common TRAEs of any grade (20%) were hypertension (36%), diarrhea (35%), fatigue (30%), decreased appetite (28%), hypothyroidism (25%), palmar-plantar erythrodysesthesia syndrome (23%), decreased weight (22%), dysphonia (21%), increased aspartate aminotransferase (20%) and proteinuria (20%).

KEYNOTE-146/Study 111 Trial Design and Data from the RCC Cohort (Abstract #5008)

KEYNOTE-146/Study 111 (ClinicalTrials.gov, NCT02501096) is a Phase 1b/2, open-label, single-arm trial evaluating the KEYTRUDA plus LENVIMA combination in patients with selected solid tumors. Results from the RCC cohort of the Phase 2 part of the study are based on 104 patients with metastatic ccRCC with disease progression following PD-1/PD-L1 immune checkpoint inhibitor therapy using RECIST v1.1 criteria. Patients were treated with KEYTRUDA 200 mg intravenously every three weeks in combination with LENVIMA 20 mg orally once daily until unacceptable toxicity or disease progression. The primary endpoint is ORR at week 24 by immune-related RECIST (irRECIST) per investigator review. Secondary endpoints include ORR, PFS, OS, safety and tolerability for a maximum of 35 cycles/treatments (approximately two years).

At data cutoff (Apr. 9, 2020), results from the Phase 2 part of the study showed the KEYTRUDA plus LENVIMA combination demonstrated an ORR at week 24 of 51% (95% CI: 41-61) by irRECIST per investigator review. As assessed by irRECIST per investigator review, ORR was 55% (95% CI: 45-65), with a partial response rate of 55%, a stable disease rate of 36% and a progressive disease rate of 5% (5% were not evaluable). Median DOR was 12 months (95% CI: 9-18). Median PFS was 11.7 months (95% CI: 9.4-17.7), and the 12-month PFS rate was 45% (95% CI: 32-57). Median OS was not reached (NR) (95% CI:16.7-NR), and the 12-month OS rate was 77% (95% CI: 67-85).

As assessed by RECIST v1.1 per investigator review, ORR was 52% (95% CI: 42-62), with a partial response rate of 52%, a stable disease rate of 38% and a progressive disease rate of 6% (5% were not evaluable). Median DOR was 12 months (95% CI: 9-18). Median PFS was 11.3 months (95% CI: 7.6-17.7), and the 12-month PFS rate was 44% (95% CI: 31-55).

TRAEs led to discontinuation of KEYTRUDA and LENVIMA in 15% of patients, discontinuation of KEYTRUDA in 12% of patients, and discontinuation of LENVIMA in 12% of patients (2% due to proteinuria). The most common TRAEs that led to dose reduction of LENVIMA were fatigue (14%), diarrhea (10%) and proteinuria (9%). Grade 4 TRAEs included lipase increased, diverticulitis, large intestine perforation and myocardial infarction, and there were two Grade 5 treatment-related deaths of upper gastrointestinal hemorrhage and sudden death. The most common TRAEs of any grade (20%) were fatigue (53%), diarrhea (46%), proteinuria (39%), dysphonia (35%), hypertension (34%), nausea (32%), stomatitis (32%), arthralgia (29%), decreased appetite (28%), palmar-plantar erythrodysesthesia syndrome (25%), hypothyroidism (23%) and headache (22%).

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Originally posted here:
KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination Demonstrated Clinically Meaningful Tumor Response Rates in Unresectable Hepatocellular...

BAR HARBOR Research by scientists at the MDI Biological Laboratoryis opening up new approaches to promoting tissue regeneration in organs damaged by disease or injury.

In recent years, research in regenerative biology has focused on stem cell therapies that reprogram the bodys own cells to replace damaged tissue, which is a complicated process because it involves turning genes in the cells nucleus on and off.

A recent paper in the journal Genetics by MDI Biological Laboratory scientist Elisabeth Marnik, Ph.D., a postdoctoral fellow in the laboratory of Dustin Updike, Ph.D., offers insight into an alternate pathway to regeneration: by recreating the properties of germ cells.

Germ cells, which are the precursors to the sperm and egg, are considered immortal because they are the only cells in the body with the potential to create an entirely new organism. The stem cell-like ability of germ cells to turn into any type of cell is called totipotency.

By getting a handle on what makes germ cells totipotent, we can promote regeneration by unlocking the stem cell-like properties of other cell types, said Updike. Our research shows that such cells can be reprogrammed by manipulating their cytoplasmic composition and chemistry, which would seem to be safer and easier than changing the DNA within a cells nucleus.

Using the tiny, soil-dwelling nematode worm, C. elegans, as a model, the Updike lab studies organelles called germ granules that reside in the cytoplasm (the contents of the cell outside of the nucleus) of germ cells. These organelles, which are conserved from nematodes to humans, are one of the keys to the remarkable attributes of germ cells, including the ability to differentiate into other types of cells.

In their recent paper entitled Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in Caenorhabditis elegans P Granules, Updike and his team describe the intriguing and elusive role of Vasa proteins within germ granules in determining whether a cell is destined to become a germ cell with totipotent capabilities or a specific type of cell, like those that comprise muscle, nerves or skin.

Because of the role of Vasa proteins in preserving totipotency, an increased understanding of how such proteins work could lead to unprecedented approaches to de-differentiating cell types to promote regeneration; or alternatively, to new methods to turn off totipotency when it is no longer desirable, as in the case of cancer.

The increase in chronic and degenerative diseases caused by the aging of the population is driving demand for new therapies, said MDI Biological Laboratory President Hermann Haller, M.D. Dustins research on germ granules offers another route to repairing damaged tissues and organs in cases where therapeutic options are limited or non-existent, as well as an increased understanding of cancer.

Because of the complexity of the cellular chemistry, research on Vasa and other proteins found in germ granules is often overlooked, but that is rapidly changing especially among pharmaceutical companies as more scientists realize the impact and potential of such research, not only for regenerative medicine but also for an understanding of tumorigenesis, or cancer development, Updike said.

Recent research has found that some cancers are accompanied by the mis-expression of germ granule proteins, which are normally found only in germ cells. The mis-expression of these germ-granule proteins seems to promote the immortal properties of germ cells, and consequently tumorigenesis, with some germ-granule proteins now serving as prognosis markers for different types of cancer, Updike said.

Updike is a former postdoctoral researcher in the laboratory of Susan Strome, Ph.D., at University of California, Santa Cruz. Strome, who was inducted into the National Academy of Sciences last year, first discovered P granules more than 30 years ago. She credits Updike, who has published several seminal papers on the subject, with great imagination, determination and excellent technical skill in the pursuit of his goal of elucidating the function and biochemistry of these tiny organelles.

The lead author of the new study from the Updike laboratory, Elisabeth A. Marnik, Ph.D., will be launching her own laboratory at Husson University in Bangor, Maine, this fall. Other contributors include J. Heath Fuqua, Catherine S. Sharp, Jesse D. Rochester, Emily L. Xu and Sarah E. Holbrook. Their research was conducted at the Kathryn W. Davis Center for Regenerative Biology and Medicine at the MDI Biological Laboratory.

Updikes research is supported by a grant (R01 GM-113933) from the National Institute of General Medical Sciences (NIGMS), an institute of the National Institutes of Health (NIH). The equipment and cores used for part of the study were supported by NIGMS-NIH Centers of Biomedical Research Excellence and IDeA Networks of Biomedical Research Excellence grants P20 GM-104318 and P20 GM-203423, respectively.

We aim to improve human health and healthspan by uncovering basic mechanisms of tissue repair, aging and regeneration, translating our discoveries for the benefit of society and developing the next generation of scientific leaders. For more information, please visitmdibl.org.

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Research at MDI Biological Laboratory explores novel pathways of regeneration and tumorigenesis - Bangor Daily News