The change in the prevalence of HHD

At the global level, the prevalence of HHD increased by 137.91% from 7.82 million in 1990 to 19.60 million in 2019 (Fig.1A, Table S1). The prevalence rate went up year by year, while the ASPR was relatively stable (Fig. 1C). The ASPR was 233.77 (95% UI=170.52312.9) per 100,000 population in 2019, which increased slightly compared with that in 1990 with an EAPC of 0.17 (95% UI=0.150.18) (Fig. 1C, Tables S2 and S3). Compared with the ASPR trend of the female subjects (EAPC, 0.28, 95% UI=0.260.30), the trend of the male subjects was more stable during the study period (EAPC, 0.02, 95% UI=0.000.04, Table S3).

The global trend of hypertensive heart disease from 1990 to 2019. The number of prevalence (A), death (D), and DALY (G). The rate of prevalence (B), death (E), and DALY (H). Age-standardized rate of prevalence (C), death (F), and DALY (I). Dashed lines represent 95% uncertainty interval; DALY, disability adjusted life-year

HHD occurred mostly in people aged over 65 (Fig. S1A). We also found that the ASPR increased with age growth for both men and women in 1990 and 2019. The female prevalence rate was much higher than male in people aged over 80 during 2019, yet there was a similar prevalence rate for aged men and women in 1990 (Fig.2).

The gender-specific global prevalence, death, and DALY rate of hypertensive heart disease in 1990 and 2019. The vertical axis represents DALY, death, and prevalence rate (per 100,000 population). DALY, disability adjusted life-year

Among 25 GBD regions, top three regions with the highest prevalence cases were Asia, East Asia, and America. In addition, the three regions with the highest ASPR were East Asia (426.15, 95% UI=306.64574.76), Oceania (344.91, 95% UI=248.54477.87), and Southeast Asia (334.77, 95% UI=244.81451.58) (Table S4). At the national level, China carried the highest HHD prevalence, followed by the United States of America and India (Fig. S2A). The highest ASPR of HHD occurred in Cook Islands, Jordan, Kuwait and Seychelles (Fig. S2C).

A total of 1.16 (95% UI=0.861.28) million people were estimated to experience HHD associated deaths worldwide in 2019, which increased from 0.65 (95% UI=0.530.73) million death cases in 1990 (Table S1). The ASDR in females was 15.05 (95% UI=11.5117.09) per 100,000 population in 2019, which was moderately higher than that in males (14.95, 95% UI=10.3216.75) (Table S2). Although the number of HHD deaths grew up dramatically during 19902019, the trend of death rate was relatively stable and the global ASDR declined with a negative value of EAPC (0.74, 95% UI=-0.92--0.58) (Fig. 1D, E, and F, Table S3). Meanwhile, the male and female ASDR shared a similar trend (EAPC for men, 0.72, 95% UI=-0.95--0.50; EAPC for women, 0.79, 95% UI=-0.93--0.65).

For both men and women, age-specific distribution of death rate remained stable in 1990 and 2019 (Fig. 2). Like HHD prevalence, people aged over 65 were more likely to suffer HHD deaths (Fig. S1B).

At the regional level, Central Sub-Saharan Africa, Eastern Sub-Saharan Africa, North Africa and Middle East had the highest ASDR; Australasia, high-income Asia Pacific and Eastern Europe were the three regions with the lowest ASDR (Table S5). At the national level, China carried the highest HHD death burden, followed by India and the Untied States of America (Fig. S2D). Bulgaria, Afghanistan, and Central African Republic were the three countries with highest ASDR (Fig. S2F).

A total of 21.50 (95% UI=16.4023.90) million DALYs were estimated on a global scale in 2019, and 13.94 (95% UI=11.3115.65) DALYs in 1990 (Table S1). There was a consistent rise in DALY number (Fig. 1G). However, DALY rate declined between 1990 and 2005, then ascended during 20062019 (Fig. 1H). In addition, it shown a persistent decline for the age-standardized DALY rate over the 30years (Fig. 1I).

The age-standardized DALY rate in men was 277.86 (95% UI=199.58311.14) per 100,000 population in 2019, which was higher than that in women (256.81, 95% UI=205.22291.98) (Table S2). The DALY rate distribution for males and females in 2019 was similar to that in 1990 (Fig. 2). In 2019, the age-specific trends of DALY rate attributed to HHD were similar for both sexes.

On the observation of the regions scale, Central Sub-Saharan Africa, Eastern Sub-Saharan Africa, and Oceania were the three regions with the highest age-standardized DALY rates (Table S5). It revealed a considerable national disparity in the burden of HHD. DALY numbers varied more than 10-fold between countries (Fig.3A). China had the highest HHD DALY number, followed by India and Indonesia (Fig. 3D). After adjusting population, Bulgaria, Estonia, and Cook Islands were the three countries with the highest rate of DALYs (Fig. 3B and E). After adjusting for age and population, Afghanistan, Cook Islands, and Central African Republic had the highest age-standardized DALY rates (Fig. 3C and F).

Global map of the disease burden of hypertensive heart disease (A, DALY number; B, DALY rates; C, Age-standardized DALY rates) and the top 20 countries with disease burden (D, DALY number; E, DALY rates; F, Age-standardized DALY rates)

The drift of HHD-related ASPR, ASDR, and age-standardized DALYs rate among five SDI quintiles were presented in Fig.4. The ASPR of HHD was highest in the middle SDI region, and the lowest in the high SDI region between 1990 and 2019 (Fig. 4A). It was interesting to note that, as opposed to the regions with other SDI, the middle SDI region presented a descending trend of ASPR (EAPC, 0.24, 95% UI=-0.2--0.20) (Table S3). ASDR and age-standardized DALY rate decreased the fastest in the middle SDI region (EAPC, 1.58, 95% UI=-1.98--1.20 for ASDR; EAPC, 1.74, 95% UI=-2.11--1.41 for age-standardized DALY rate) (Table S3, Fig. 4B and C). In the middle SDI region, the trend of ASDR and age-standardized DALY rate presented undulating curves (Fig. 4B and C). Compared with a downward trend for females (EAPC, 0.28, 95% UI=-0.4--0.11), male age-standardized DALY rate showed an upward tendency in the high SDI region (EAPC, 0.34, 95% UI=0.110.57).

The age-standardized prevalence, death, and DALY rate for hypertensive heart disease by different SDI regions, 19902019. ASPR, age-standardized prevalence rate; ASDR, age-standardized death rate; DALY, disability adjusted life-year; SDI, socio-demographic index

ASPR, ASDR, and age-standardized DALY rate of HHD stratified by SDI were shown in Fig.5. ASPR of HHD rose before SDI value of 0.4 and then start to decrease (Fig. 5A). There was a negative and significant Pearsons correlation between HHD disease burden and SDI (r=0.74, 95% CI=-0.77--0.70, p<0.001, for age-standardized DALY rate; r=0.70, 95% CI=-0.74--0.66, p<0.001, for ASDR) (Fig. 5C). The univariate linear regression indicated that many socioeconomic variables (HDI, IHDI, SDI, HAQ, population with at least some secondary education, life expectancy, and physicians per 10,000 people) had a significantly negative correlation with age-standardized DALY rate (all p<0.001, Table1).

The trend in ASPR (A), ASDR (B), age-standardized DALY rate (C) of hypertensive heart disease in 21 regions based on SDI. Expected values are shown as the dark blue line. ASPR, age-standardized prevalence rate; ASDR, age-standardized death rate; DALY, disability adjusted life-year; SDI, socio-demographic index

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Global, regional, and national burden of hypertensive heart disease during 19902019: an analysis of the global burden of disease study 2019 - BMC...

Cardiac Stem Cells Comments Off on Global, regional, and national burden of hypertensive heart disease during 19902019: an analysis of the global burden of disease study 2019 – BMC… | April 29th, 2022

By Steve Gorman

(Reuters) The first all-private astronaut crew to fly aboard the International Space Station (ISS) headed for splashdown Monday off the coast of Florida, wrapping up a two-week mission that NASA has touted as a landmark in commercial spaceflight.

A SpaceX Crew Dragon capsule carrying the four-man team of Houston-based startup Axiom Space Inc began its return flight about 9 p.m. EDT Sunday (0100 Monday GMT) as it undocked from the space station orbiting about 250 miles (420 km) above Earth.

The Crew Dragon was expected to parachute into the Atlantic around 1 p.m. EDT on Monday (1700 GMT), capping a 16-hour ride home from orbit that had been postponed for several days because of unfavorable weather.

The multinational Axiom team was led by Spanish-born retired NASA astronaut Michael Lopez-Alegria, 63, the companys vice president for business development. His second-in-command was Larry Connor, 72, a technology entrepreneur and aerobatics aviator from Ohio designated the mission pilot.

Joining them as mission specialists were investor-philanthropist and former Israeli fighter pilot Eytan Stibbe, 64, and Canadian businessman and philanthropist Mark Pathy, 52.

Launched from NASAs Kennedy Space Center on April 8, they spent 15 days aboard the space station with the seven regular, government-paid ISS crew members: three American astronauts, a German astronaut and three Russian cosmonauts.

The ISS has hosted several wealthy space tourists from time to time over the years.

But the Axiom quartet was the first all-commercial team ever welcomed to the space station as working astronauts, bringing with them 25 science and biomedical experiments to conduct in orbit. The package included research on brain health, cardiac stem cells, cancer and aging, as well as a technology demonstration to produce optics using the surface tension of fluids in microgravity.

Axiom, NASA and SpaceX have hailed the mission as a milestone in the expansion of privately funded space-based commerce, constituting what industry insiders call the low-Earth orbit economy, or LEO economy for short.

It was the sixth human spaceflight for SpaceX in nearly two years, following four NASA astronaut missions to the ISS and the Inspiration 4 flight in September that sent an all-private crew into Earth orbit for the first time, though not to the space station.

SpaceX, the private rocket company founded by Tesla Inc electric carmaker CEO Elon Musk, has been hired to fly three more Axiom astronaut missions to ISS over the next two years. The price tag for such outings is high.

Axiom charges customers $50 million to $60 million per seat, according to Mo Islam, head of research for the investment firm Republic Capital, which holds stakes in both Axiom and SpaceX.

Axiom also was selected by NASA in 2020 to build a new commercial addition to the space station, which a U.S.-Russian-led consortium of 15 countries has operated for more than two decades. Plans call for the Axiom segment to eventually replace the ISS when the rest of the station is retired around 2030.

(Reporting by Steve Gorman in Los Angeles. Editing by Gerry Doyle)

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First all-private astronaut team aboard space station heads for splashdown - KFGO

Cardiac Stem Cells Comments Off on First all-private astronaut team aboard space station heads for splashdown – KFGO | April 29th, 2022

Inflammation represents one of the leading drivers of disease. Biotech company 180 Life Sciences is developing novel, anti-TNF therapies for treating distinct inflammatory diseases.

DocWire News spoke to James Woody, CEO of 180 Life Sciences, to learn more about the company, its mission, its treatment assets, and current clinical trials its involved in.

*Interview recorded in March 2022.

DocWire News:Can you give us some background on yourself, and the company, 180 Life Sciences?

James Woody:So by background, Im a pediatric immunologist, and in my prior life, I was Chief Scientific Officer of a company called Centocor, which was one of the very early biotech companies. And we were the first ones ever to make a anti-TNF antibody and to test it in patients, and we were able to show that it was remarkably effective in patients with rheumatoid arthritis, Crohns disease and psoriasis and ulcerative colitis. And that actually began the pretty much the whole antibody based biologics industry. We were the first ones to do this with a humanized antibody.

I went on from there to run a pharmaceutical company called Syntex, former Syntex that was after Roche bought it and did that for eight years, we invented a lot of small molecules. And then I went on to start a company in oncology, cancer stem cells. And from there I went over to the dark side and joined a venture capital group and helped start companies for about 10 years and some of them are really successful. Some of them are okay and some crashed and burned, but thats the nature of the business. And then more recently I helped start a couple companies on my own. And then I was approached by the founders of 180 LS to help them out and also to be CEO of their company, so thats how I came to be CEO of 180 Life Sciences.

180 Life Sciences is repurposing anti-TNF for unmet needs. What is anti-TNF?

So in your body, you have lots of protein circulating around in your blood. These tell the body cells what to do, and some of them are called cytokines and cytokines are the ones that kind of tell your immune system what to do. And theres quite a lot of these. And theres some of them that are very good. Theres some of them that are bad actors and one of them is called tumor necrosis factor. It was named that totally by accident because it seemed to eliminate tumors in mice, but thats never been able to be shown in humans, but the name has stuck with it. So tumor necrosis factor is the thing that causes some types of inflammation, if theres an overproduction. For example, in rheumatoid arthritis, its the tumor necrosis factor that drives the destruction of the joints of your fingers and knees and shoulders and everything, so its a destructive cytokine. And what we did is we made a specialized antibody against TNF that binds it up and blocks it and prevents it from causing the inflammation. And that was the basis of infliximab or Remicade that we discovered from Centocor.

What is Dupuytrens disease, how is it characterized?

Dupuytrens Contracture is kind of a chronic disease, but it affects quite a lot of people, maybe 16 or 20 million in the US, same in Europe. It starts out as a small nodule in your palm. And over time, maybe a couple of years, some faster, some slower, it begins to form cords underneath the palm of your hand, it pulls your fingers together and contracts them. Sometimes this is inherited in families and sometimes it just occurs. So what happens is that this nodule starts, and as I said, over time, the fingers become contracted. So theres no therapies for the early stage when the nodules just form, but thats the basis of what were doing, Ill talk about that in a minute.

Later on, after the fingers are already contracted and you have the disability, you cant button your clothes, you cant type with that hand. You cant do many of the things that you like to do with your hand. Theres several therapies that they try. One of them is injecting a collagenase thats partially effective, but they all, about half of those recur. You can try to disrupt these cords with a needle called needle aponeurectomy or alternatively, what happens is you end up going to surgery and they cut these cords out. Ironically, my wife had this and went through a whole year of steroid injections into her hand, finally had to have the surgery. So Im familiar with the process. But thats what happens, and I think people, as soon as the nodule forms, people these days, because they have Dr. Google, can immediately know whats going to happen in the long run, so the information out there is quite impressive.

180 Life Sciences recently completed a Phase 2 study for Dupuytrens. Tell us about the study protocol, the drug used and other updates on the study.

Our colleague in England, Dr. Jagdeep Nanchahal, was able to look at Dupuytrens Contracture and especially the nodules, and through a series of very elegant experiments, he was able to show that the nodule was driven by the TNF, the bad actor. And in this case, the inflammation caused the fibrosis that were talking about, that leads to the finger contracture. And so he was able to work out that if you inject anti-TNF into this nodule, you can impact the course of the disease.

And so he did a very large trial of about 150 patients in the UK and was able to inject anti-TNF into the nodules of their hands. And in that trial, which took over a year, there were three or four injections, but we were able to show that both the primary and secondary endpoints of the trial were met and the endpoints had to do with the size of the nodule, whether it was growing, whether it was shrinking, whether it was harder or whether it was softer or whether the fingers were contracting, all of that, but we met the primary endpoints and the full publication with all the details will be out, hopefully in the next couple of months.

You have another trial planned for Frozen Shoulder. What is Frozen Shoulder, and how will the trial aim to address it?

Yes, Frozen Shoulder is another kind of inflammatory condition where fibrosis forms in the shoulder. And it initially starts out as being extremely painful. And that goes on for several months and then eventually the pain subsides, but the shoulder becomes totally immobile. And eventually you have to have surgery to remove the fibrotic tissues. Interestingly enough, this occurs more common in patients with diabetes, but about half of those patients also have Dupuytrens. And so we think that the fibrosis in the Dupuytrens and the fibrosis in the shoulder is the same mechanism. And so Dr. Nanchahal will be injecting anti-TNF into the shoulder very early, as soon as the pain is evident, then hell try to inject anti-TNF and maybe relieve the pain and also the formation of the fibrosis, so that one can avoid the surgery, which is actually quite expensive. And also, theres quite a long course of physical therapy after the surgery, so its something youd like to avoid. And so were trying to treat patients both with Dupuytrens and Frozen Shoulder before the disability develops.

A third program, which is soon to be clinical, is anti-TNF for post-operative cognition delirium or POCD. Tell me about POCD, and the preliminary research that led the team to pursue this indication?

We know that now that theyre doing fairly aggressive surgery in older patients, either hip replacements or emergency hip corrections or CABG procedure, coronary artery bypass graft, or cardiac surgery, that a fair percentage of these people after the surgery, just have a foggy brain. And the fog goes on for some time and we call it postoperative cognitive dementia, as the technical term. And in some patients, maybe 15 or 20%, it doesnt go away. And they end up in nursing homes and they actually dont live very long after that. And so our colleagues in the UK, Dr. Nanchahal and Dr. Feldmann and his colleagues, have shown that during the surgery, any kind of aggressive surgery, that TNF is released from the tissue damage, and the TNF goes to the brain and opens it up and lets inflammatory cells get into the area of the brain thats where your cognitive areas are, and so that leads to the dementia.

And in the past, theyve thought this all had to do with the anesthesia, but we think its the TNF thats actually causing this dementia going forward. And so were actually going to do a trial in patients that are having their hip repaired that are older, and were going to administer one dose of anti-TNF just before the surgery starts with a view towards preventing the dementia going forward. So this will be a long trial, but if it works, itll be something that everybody who goes into major surgery would want to have. So its another exciting opportunity for 180 LS and our investigators.

180 Life Sciences recently announced licensing of a compound called HMGB1. Tell us more about HMGB1 and the companys plans for it.

The company is also working on other areas of fibrosis, not just Dupuytrens Contracture and Frozen Shoulder, but other areas like liver fibrosis, which occurs with NASH. And we are working on ways to prevent that as well, much like were working on Dupuytrens and Frozen Shoulder. The fibrosis in the liver is really hard to reverse, and there are no real agents that do that, but theres a lot of people trying different things. Now what the HMGB-1 does, it doesnt change the fibrosis, but once the fibrosis is stopped, it could help the liver cells to regenerate. So this is kind of a regenerative medicine. It makes the tissues regenerate, whether its heart or whether its liver or whether its lung or whatever. And so its going to be used after the fibrosis is stopped. And so thats kind of what were interested in. And were just getting that program off the ground and making the initial compounds to do our testing.

Any closing thoughts?

Well, Id like to talk about our team. The company was founded by Dr. Mark Feldmann, who was the one, he was the original person who figured out that TNF was causing the joint destruction and arthritis, and with he and I and others, that actually did the very first trials ever. And this was done in patients with wheelchairs, and they actually got up out of their wheelchairs and walked around. It was a phenomenal moment. We had no idea it would work that well. And some of them actually did a pirouette down some stairs. We have videos of this. So its kind of like The Awakening movie where they gave them the L-DOPA and they all woke up. Well, in this case, they got up out of their wheelchairs and theres no patients in wheelchairs with rheumatoid arthritis in the whole world because of that drug, and the ones that followed on.

The current Humira from AbbVie is the preferred one. But the whole idea and concept, we started back then. Other founders, Dr. Larry Steinman, he and Mark put 180 LS together. And he developed Tysabri, the very first drug to help MS patients. And it was another phenomenal discovery that he made. And hes also working on MS and other areas. But so we have the leaders in inflammation as the people who actually founded the company. So its a pleasure to work with them. Ive been acquainted with them off and on for the past, maybe 25 years, so working with them again is a real pleasure.

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James Woody, CEO of 180 Life Sciences: Developing New Therapies to Treat Inflammatory Diseases - DocWire News

Cardiac Stem Cells Comments Off on James Woody, CEO of 180 Life Sciences: Developing New Therapies to Treat Inflammatory Diseases – DocWire News | April 29th, 2022

Stem cells are key building blocks for the human body. At the start of life, they divide over and over again to create a fully developed baby from an embryo. Many individuals now even turn to services that store and preserve umbilical cords should a person ever be in need.

Stem cells have the potential to develop into different types of cells in the body, serving as a repair system of sorts for damaged or lost cells. In recent decades, scientists have shown the miraculous ways of medicine through stem cell treatments.

So just how are doctors using stem cells to treat and help heal people battling various ailments? Heres a look at five studies published on StudyFinds that demonstrate the wondrous ways of stem cell treatments.

A heart condition called dilated cardiomyopathy, or DCM, weakens muscles of the ventricles, which causes heart failure and often death in children. Currently, the only cure is a heart transplant, which can take long periods of time to find an acceptable donor and increases the risk of rejection of the donor tissue. One study finds that stem cell therapy could help DCM patients survive longer while awaiting a transplant or potentially eliminate the need for a new heart entirely.

Cardiac stem cells called cardiosphere-derived cells (CDCs) have proven to be effective at treating certain heart conditions. The CDCs grow into tissue cells of the heart and can counter the effects of DCM. To test the safety of the CDC therapy, a team of scientists at Okayama University in Japan demonstrated the efficacy of CDCs in tissue damaged from DCM. For the study, DCM symptoms were induced in pigs, after which CDCs were administered in various doses for treatment. In a control group, some pigs were given a placebo.

Results showed thickening of the heart muscle in pigs who were given the stem cell treatment. This allows increased blood flowto the rest of the body, thereby effectively repairing the damaged tissue. Due to the dosage used in animal trials, researchers could estimate the proper dosage for human trials.

The first of these included 5 younger patients who were diagnosed with DCM. Injections of CDCs resulted inbetter heart function without any serious side effects. Thus, scientists believe this type of treatment could minimize the need for heart transplants and allow DCM patients to have normal lives.

READ MORE: Stem cell treatment shows promise as treatment for rare heart condition in children

Although their use is sometimes controversial, scientists often look at stem cells as a potential miracle cure for many conditions. One study finds stem cells from a babys umbilical cord may save the most at risk of dying from COVID-19. A treatment derived from non-altered versions of these stem cells significantly improves the survival rate among coronavirus patients already on a ventilator.

In a double-blind, controlled, randomized study, 40 adultpatients in intensive careand on a ventilator received the treatment intravenously. The infusions contained stem cells coming from the connective tissue of a human umbilical cord. Half of the patients received infusions not containing stem cells to serve as a control group.

Results reveal survival rates climbed by 2.5 times among patients receiving stem cells. Those with a pre-existing health problem, making them high-risk for COVID, saw their changes of beating coronavirus jump by 4.5 times. Moreover, the study says the stem cell infusions did not cause any life-threatening complications or allergic reactions.

READ MORE: Stem cells from a babys umbilical cord doubles survival chances among COVID patients

In the fight against heart disease, a new super-weapon is now even closer to deployment, and its capabilities are turning out to be beyond expectations. A study aimed at combating heart disease finds that stem cells are not only showing promise in treating heart failure, but in rats are actually reversing problems associated with old age.

The specific type of stem cells used in the study are cardiosphere-derived cells, or CDCs. While the latest research involving CDCs indicates possibilities that have previously been in the realm of science fiction, the scientists leading the charge urge restraint in face of the excitement.

Nevertheless, the latest results of stem cell infusions in rats are startling. Not only did rats that received the CDCs experience improved heart function, they also had lengthened heart cell telomeres. Moreover, the rats that received the treatment also had their exercise capacity increase by about 20 percent. They also regrew hair faster than rats that didnt receive the cells.

Still, the doctors and scientists working to push the frontier of medicine forward are very optimistic about the real possibilities of the therapy. Researchers of the study said they are also studying the use of stem cells in treating patients with Duchenne muscular dystrophy and patients with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients.

READ MORE: Study: Cardiac stem cell injections reverse effects of aging

A new biomaterial can help regenerate tissue in people dealing with chronic lower back pain and spinal issues. A recent study finds the secret to this breakthrough therapy is all in the hiPS. Not thosehips, but human induced pluripotent stem cells.

The study explains that a common cause of lower back pain is the degeneration of intervertebral discs (IVDs). These discs sit between the vertebrae in the spine and help give the spinal column its flexibility. Severe IVD degeneration eventually leads to spinal deformity without treatment. In this study, scientists used cartilage tissue derived from stem cells to build back lost IVDs in lab rats.

Study authors used induced pluripotent stem cells (iPSCs) during their experiments. Importantly, scientists are capable of turning iPSCs into chondrocytes cells that produce and maintain cartilage. Previous studies have successfully used this same method to treat cartilage defects in animals. In the new study, researchers created human iPSC-derived cartilaginous tissue (hiPS-Cart) that they implanted into rats with no NP cells in their intervertebral discs.

Findings reveal that the hiPS-Cart implanted in the rats was able to survive and be maintained. IVD and vertebral bone degeneration were prevented. The researchers also assessed the mechanics and found that hiPS-Cart was able to revert these properties to similar levels observed in the control rats.

READ MORE: Stem cell cure for lower back pain is all in the hiPS

Stem cells taken from deceased patients may also help in creating a cure for blindness. Retina cells from a corpse continue to survive after being transplanted into the eyes of monkeys, scientists say.

RPE dysfunction is a leading cause of blindness, including causing disorders likemacular degeneration, which affects around 200 million people worldwide. Now, for the first time, scientists have successfully produced retina cells in monkeys using human stem cells. Human cadaver donor-derived cells can be safely transplanted underneath the retina and replace host function, and therefore may be a promising source for rescuing visionin patients with retina diseases.

For the study, researchers transplanted stem cells from the eyes of donated bodies under the monkeys macula, the central part of the retina. Following surgery, the transplanted patches remained stable for at least three months without any serious side-effects. The RPE created by the human stem cells partially took over from the old retina cells. In addition, this could successfully support the eyes light receptorswithout causing retinal scarring.

These unique cells could serve as an unlimited resource of human RPE, whichmay restore sightfor millions of people around the world. The scientists caution that they will need to conduct more research to see how the procedure works with human transplant patients. Human trials are still a long way off.

READ MORE: Eye stem cells transplanted from corpses to live patients could cure blindness

For more information on each of these stem cell treatments, you can refer to the READ MORE links in between each section.

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Stem Cell Magic: 5 Promising Treatments For Major Medical Conditions - Study Finds

Spinal Cord Stem Cells Comments Off on Stem Cell Magic: 5 Promising Treatments For Major Medical Conditions – Study Finds | April 29th, 2022

One is that there are some people that are naturally resistant to heart attack and have lifelong, low levels of LDL, the cardiologist says. Second, there are some genes that can be switched off that lead to very low LDL cholesterol, and individuals with those genes switched off are resistant to heart attacks.

Kathiresan and his team formed a hypothesis in 2016 that if they could develop a medicine that mimics the natural protection that some people enjoy, then they might identify a powerful new way to treat and ultimately prevent heart attacks. They launched Verve in 2018 with the goal of creating a one-time therapy that would permanently lower LDL and eliminate heart attacks caused by high LDL.

The medication is targeted specifically for patients who have a genetic form of high cholesterol known as heterozygous familial hypercholesterolemia, or FH, caused by expression of a gene called PCSK9. Verve also plans to develop a program to silence a gene called ANGPTL3 for patients with FH and possibly those with or at risk of atherosclerotic cardiovascular disease.

FH causes cholesterol to be high from birth, reaching levels of 200 to 300 milligrams per deciliter. Suggested normal levels are around 100 to 129 mg/dl, and anything above 130 mg/dl is considered high. Patients with cardiovascular disease usually are asked to aim for under 70 mg/dl, but many still have unacceptably high LDL despite taking oral medications such as statins. They are more likely to have heart attacks in their 30s, 40s and 50s, and require lifelong LDL control.

The goal for drug treatments for high LDL, Kathiresan says, is to reduce LDL as low as possible for as long as possible. Physicians and researchers also know that a sizeable portion of these patients eventually start to lose their commitment to taking their statins and other LDL-controlling medications regularly.

If you ask 100 patients one year after their heart attack what fraction are still taking their cholesterol-lowering medications, its less than half, says Kathiresan. So imagine a future where somebody gets a one-time treatment at the time of their heart attack or before as a preventive measure. Its right in front of us, and its something that Verve is looking to do.

In late 2020, Verve completed primate testing with monkeys that had genetically high cholesterol, using a one-time intravenous injection of VERVE-101. It reduced the monkeys LDL by 60 percent and, 18 months later, remains at that level. Kathiresan expects the LDL to stay low for the rest of their lives.

Verves gene editing medication is packaged in a lipid nanoparticle to serve as the delivery mechanism into the liver when infused intravenously. The drug is absorbed and makes its way into the nucleus of the liver cells.

Verves program targeting PCSK9 uses precise, single base, pair base editing, Kathiresan says, meaning it doesn't cut DNA like CRISPR gene editing systems do. Instead, it changes one base, or letter, in the genome to a different one without affecting the letters around it. Comparing it to a pencil and eraser, he explains that the medication erases out a letter A and makes it a letter G in the A, C, G and T code in DNA.

By making that simple change from A to G, the medication switches off the PCSK9 gene, automatically lowering LDL cholesterol.

Once the DNA change is made, all the cells in the liver will have that single A to G change made, Kathiresan says. Then the liver cells divide and give rise to future liver cells, but every time the cell divides that change, the new G is carried forward.

Additionally, Verve is pursuing its second gene editing program to eliminate ANGPTL3, a gene that raises both LDL and blood triglycerides. In 2010, Kathiresan's research team learned that people who had that gene completely switched off had LDL and triglyceride levels of about 20 and were very healthy with no heart attacks. The goal of Verves medication will be to switch off that gene, too, as an option for additional LDL or triglyceride lowering.

Success with our first drug, VERVE-101, will give us more confidence to move forward with our second drug, Kathiresan says. And it opens up this general idea of making [genomic] spelling changes in the liver to treat other diseases.

The approach is less ethically concerning than other gene editing technologies because it applies somatic editing that affects only the individual patient, whereas germline editing in the patients sperm or egg, or in an embryo, gets passed on to children. Additionally, gene editing therapies receive the same comprehensive amount of testing for side effects as any other medicine.

We need to continue to advance our approach and tools to make sure that we have the absolute maximum ability to detect off-target effects, says Euan Ashley, professor of medicine and genetics at Stanford University and founding director of its Center for Inherited Cardiovascular Disease. Ashley and his colleagues at Stanfords Clinical Genomics Program and beyond are increasingly excited about the promise of gene editing.

We can offer precision diagnostics, so increasingly were able to define the disease at a much deeper level using molecular tools and sequencing, he continues. We also have this immense power of reading the genome, but were really on the verge of taking advantage of the power that we now have to potentially correct some of the variants that we find on a genome that contribute to disease.

He adds that while the gene editing medicines in development to correct genomes are ahead of the delivery mechanisms needed to get them into the body, particularly the heart and brain, hes optimistic that those arent too far behind.

It will probably take a few more years before those next generation tools start to get into clinical trials, says Ashley, whose book, The Genome Odyssey, was published last year. The medications might be the sexier part of the research, but if you cant get it into the right place at the right time in the right dose and not get it to the places you dont want it to go, then that tool is not of much use.

Medical experts consider knocking out the PCSK9 gene in patients with the fairly common genetic disorder of familial hypercholesterolemia roughly one in 250 people a potentially safe approach to gene editing and an effective means of significantly lowering their LDL cholesterol.

Nurse Erin McGlennon has an Implantable Cardioverter Defibrillator and takes medications, but she is also hopeful that a gene editing medication will be developed in the near future.

Erin McGlennon

Mary McGowan, MD, chief medical officer for The Family Heart Foundation in Pasadena, CA, sees the tremendous potential for VERVE-101 and believes patients should be encouraged by the fact that this kind of research is occurring and how much Verve has accomplished in a relatively short time. However, she offers one caveat, since even a 60 percent reduction in LDL wont completely eliminate the need to reduce the remaining amount of LDL.

This technology is very exciting, she said, but we want to stress to our patients with familial hypercholesterolemia that we know from our published research that most people require several therapies to get their LDL down., whether that be in primary prevention less than 100 mg/dl or secondary prevention less than 70 mg/dl, So Verves medication would be an add-on therapy for most patients.

Dr. Kathiresan concurs: We expect our medicine to lower LDL cholesterol by about 60 percent and that our patients will be on background oral medications, including statins that lower LDL cholesterol.

Several leading research centers are investigating gene editing treatments for other types of cardiovascular diseases. Elizabeth McNally, Elizabeth Ward Professor and Director at the Center for Genetic Medicine at Northwestern Universitys Feinberg School of Medicine, pursues advanced genetic correction in neuromuscular diseases such as Duchenne muscular dystrophy and spinal muscular atrophy. A cardiologist, she and her colleagues know these diseases frequently have cardiac complications.

Even though the field is driven by neuromuscular specialists, its the first therapies in patients with neuromuscular diseases that are also expected to make genetic corrections in the heart, she says. Its almost like an afterthought that were potentially fixing the heart, too.

Another limitation McGowan sees is that too many healthcare providers are not yet familiar with how to test patients to determine whether or not they carry genetic mutations that need to be corrected. We need to get more genetic testing done, she says. For example, thats the case with hypertrophic cardiomyopathy, where a lot of the people who probably carry that diagnosis and have never been genetically identified at a time when genetic testing has never been easier.

One patient who has been diagnosed with hypertrophic cardiomyopathy also happens to be a nurse working in research at Genentech Pharmaceutical, now a member of the Roche Group, in South San Francisco. To treat the disease, Erin McGlennon, RN, has an Implantable Cardioverter Defibrillator and takes medications, but she is also hopeful that a gene editing medication will be developed in the near future.

With my condition, the septum muscles are just growing thicker, so Im on medicine to keep my heart from having dangerous rhythms, says McGlennon of the disease that carries a low risk of sudden cardiac death. So, the possibility of having a treatment option that can significantly improve my day-to-day functioning would be a major breakthrough.

McGlennon has some control over cardiovascular destiny through at least one currently available technology: in vitro fertilization. Shes going through it to ensure that her children won't express the gene for hypertrophic cardiomyopathy.

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Podcast: Has the First 150-Year-Old Already Been Born - Leaps

Skin Stem Cells Comments Off on Podcast: Has the First 150-Year-Old Already Been Born – Leaps | April 29th, 2022

Paper Title: Identification of a retinoic acid-dependent hemogenic endothelial progenitor from human pluripotent stem cells

Journal: Nature Cell Biology

Authors:Christopher Sturgeon, PhD, Associate Professor of Cell, Developmental & Regenerative Biology and Medicine, Hematology & Medical Oncology in the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, and other coauthors.

Bottom Line:Blood-forming stem cells found in bone marrow are the life-saving component used in bone marrow transplants. However, suitable donors often cannot be found in many cases. This study reveals how the human embryo develops the precursor to blood forming stem cells, which researchers say can be used in the novel method they developed to generate blood-forming stem cells from cells in tissue culture.

The studyled by researchers from Mount Sinai and the San Raffaele Telethon Institute for Gene Therapy in Milan Italyconfirms many aspects of cell development, including origins and regulation, which are known to occur within both the mouse and human embryo. In the mammalian embryo, blood-forming stem cells emerge from a specialized cell type called hemogenic endothelium. These cells develop in response to a critical signal pathway known as retinoic acid, which is essential for growth. Their analysis found that stem cell populations derived from human pluripotent stem cells were transcriptionally similar to cells in the early human embryo.

Results: For years, researchers in the field of regenerative medicine have been able to obtain hemogenic endothelium from embryonic stem cells, but these cells do not produce blood-forming stem cells. In the embryo, blood-forming stem cell development requires signaling by retinoic acid.But, current state-of-the-art methods for deriving blood progenitors from human pluripotent stem cells do so in the absence of retinoic acid. In this latest study, researchers examined the dependence on retinoic acid in early cell types derived from human pluripotent stem cells. They performed single cell RNA sequencing of stem cells in vitro to better understand patterns of mesodermal cell types during early development. The research team identified a new strategy to obtain cells that are transcriptionally similar to those hemogenic endothelial cells found in the human embryo by stimulating a very discrete original population with retinoic acid.

Why the Research Is Interesting:This new method brings researchers and scientists closer to developing blood-forming stem cells in tissue culture, but also provides a pathway to establishing specialized blood cell types for transfusions and other treatments for cancer since the new method makings it possible to obtain the same original cells in adult blood that are found in a developing embryo.

Said Mount Sinai's Dr. Christopher Sturgeon of the research:We have made a major breakthrough in our ability to direct the development of stem cells in a tissue culture dish into cells that have the same gene expression signature as the immediate progenitor of a blood-forming stem cell found in the developing embryo. With this, now we can focus our efforts at understanding how to capture embryonic blood-forming stem cells, with the goal of using them as a substitute for bone marrow.

Researchers from the Washington University School of Medicine in St. Louis, MO contributed to this study.

###

To request a full copy of the paper or to schedule an interview with the researcher, please contact the Mount Sinai Press Office at stacy.anderson@mountsinai.org or 347-346-3390.

Nature Cell Biology

28-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -...

Bone Marrow Stem Cells Comments Off on Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -… | April 29th, 2022

There are few things more grueling than running a marathon.

One of those is battling cancer.

A La Conner native knows all about the former, having previously run the Denver Colfax Marathon. Now shes helping bring greater awareness to the latter by raising funds for the Leukemia & Lymphoma Society as she trains for the Chicago Marathon in October.

Morgan Harlan, a 2020 Baylor University grad now teaching kindergarten in Denver, is hoping to raise $4,000 for LLS by running the urban Chicago course with two friends this fall. The Chicago Marathon is typically viewed by more than a million spectators.

I hope to raise as much money as I possibly can for such a worthy cause that is so important to my family, she told the Weekly News on Friday.

Her family has seen first-hand the life-saving potential of bone marrow and blood stem cell transplants, and is committed to helping find cures and ensure access to treatments for all blood cancer patients.

Harlans grandfather, longtime La Conner resident and Dunlap Towing retiree Mit Harlan, waged a successful battle against leukemia over a decade ago.

My grandfather, said Harlan, is alive because of a stem cell transplant.

While a student at Baylor, where she was a journalism/public relations major and played club soccer, Harlan signed up for Be the Match, which connects patients with transplant donors.

As a college student with a family member who had experienced cancer, said Harlan, I thought I was doing my due diligence by signing up for the registry.

Last December, four years after joining Be the Match, Harlan flew to Seattle to donate her stem cells.

Her patient was a 65-year-old male with leukemia the same age her grandfather was when he received his transplant.

When Be the Match called to inform me that I was the match and asked me if I would be willing to donate my stem cells, Harlan added, my response was: Absolutely. I hope I can give another little girl or boy more time with their grandpa like I was given.

Harlan has not stopped there. She has taken on fundraising for the cause, doing so in a way that shows she is in it for the long run.

She has enlisted a coach, La Conner alum Carlee Daub, to help her train for Chicago. Daub is an owner of Wahoo Running, an online platform that provides coaching to runners throughout the nation.

My first marathon, Harlan recalled, I was focused on completion. I wanted to prove to myself that I had the physical and mental grit to get through 26.2 miles. The Chicago Marathon will be focused more on speed and race strategy.

As Harlan has lowered her running times, her fundraising numbers have increased.

My fundraising has gone really well because of the wonderful people around me, she said. I am very thankful to have generous family members, friends, and community members.

My original goal was to raise $2,000, Harlan explained, which I was able to raise in the first week. I have since raised my goal to $4,000.

Committing to run the Chicago Marathon on behalf of LLS is a big step for Harlan. After graduating from Burlington-Edison High School, having competed in soccer and track there, Harlan chose to go out of state for college.

I wanted to travel outside of Washington for my four years of college and live somewhere new, she said. Baylor had a great mix of academic strength, athletics success and extracurriculars.

While on the Waco, Texas campus, Harlan regularly wrote for the student newspaper, the Baylor Lariat.

Now, as she preps for the Chicago Marathon and generates support for LLS, Harlan is making rather than reporting the news.

For her, its a story whose headliner is her grandfather.

Hes one of the best humans I know, said Harlan. Growing up, he never missed a soccer match (of mine), including a tournament in Spain. Hes very giving with his time and money, especially towards charities like LLS.

Harlan, daughter of Mike and Jennifer Harlan, of Landing Road, southeast of La Conner, said the best ways to donate are through either her donation page: (https://pages.lls.org.tnt/rm.chicago22/MHarlan) or Facebook.

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La Conner native raising funds to cure blood cancer - La Conner Weekly News

Bone Marrow Stem Cells Comments Off on La Conner native raising funds to cure blood cancer – La Conner Weekly News | April 29th, 2022

Community members are speaking out about the role blood donation has played in their personal lives.

This comes as Action News Jax and our Family Focus partners have teamed up for our annual Spring Into Action Blood Drive.

Jacksonville resident Penelope McGowan told Action News Jax reporter Kennedy Dendy that having the opportunity to give blood is an honor. My father needed a life-saving procedure, so it became more important to me to start giving blood, McGowan said.

She then became a regular giver, knowing the impact donation truly has.

That allowed him the time to spend time with his grandchildren, McGowan said. He walked his granddaughter down the aisle and got to see some of his great-grandchildren.

McGowan said blood donation made that moment possible.

Now that hes passed away, I want to give that gift of time to other families, McGowan said. So, its so important to me to give blood.

RELATED: OneBlood, Action News Jax team up for the Spring into Action Blood Drive

Action News Jax also spoke with John Dean, who is a patient at the Mayo Clinic. Hes from South Carolina but has been living in Jacksonville since January.

I got the bone marrow transplant, which is basically a stem cell infusion on January 17th, Dean said. I have been dealing with myelodysplastic syndrome.

Dean said its a form of bone marrow cancer hes been battling since 2017.

During that time, I had become increasingly dependent upon blood because the syndrome destroys my bodys ability to make red blood cells, Dean said. So when the blood numbers drop, I get very very sick.

He said the transplant was designed to cut down on his need to get the blood, but that hasnt happened yet.

Ive been more blood dependent since January than I had been before I came down here, Dean said.

Dean spoke with me just moments after he received a blood transfusion at the hospital -- but he wanted one message out there.

Youre transmitting a miracle, Dean said. Im a living example of that. I would not be here were it not for the blood.

Story continues

OneBlood said to donate youll need an ID, and you must be 16 years and older.

Randy Varner donated double red blood cells at Tuesdays drive.

My wife has had to have two heart valves replaced, so shes had to have blood before at the hospital -- so I try to help out when I can, Varner said.

Varner shared that if youre able to -- you should give.

Theres nothing to it, Varner said. You go in there. You answer a few questions. You lay down. You can take a little nap if you have to.

Nicole Payne is the Senior Program and Membership Director with the Brooks Family YMCA, one of the many sites for the drive.

Theres always a lack of blood available for people that come into any traumatic situation, Payne said. We want to make sure that we can hopefully combine some of the best parts of Jacksonville -- and thats through OneBlood being here to help people have access to donate.

The Spring into Action Blood Drive kicked off Tuesday and runs through Friday.

When you donate you will receive a free t-shirt, a $20 e-gift card, and an additional gift depending on the location where you donate.

CLICK HERE to find out when and where you can donate.

STAY UPDATED: Download the Action News Jax app for live updates on breaking stories

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I would not be here were it not for the blood: Duval residents describe impact of blood donation - Yahoo News

Bone Marrow Stem Cells Comments Off on I would not be here were it not for the blood: Duval residents describe impact of blood donation – Yahoo News | April 29th, 2022

REGULATED INFORMATION

Strategic focus revised and fully focused on achieving topline results of the ALLOB Phase IIb study in tibial fractures.

Discussions for ALLOB global partnership still ongoing.

Board of Directors and Management exploring all strategic options to protect shareholder value.

Strengthening financial position with EIB agreement and private placement in 2021 and a new bond issuance foreseen in May 2022

Management to host conference call today at 3pm CEST / 9am EST - details provided below

Mont-Saint-Guibert, Belgium, 29April 2022, 7am CEST BONE THERAPEUTICS (Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today announces its business update and full year financial results for the year ending 31 December 2021, prepared in accordance with IFRS as adopted by the European Union.

Incomplete fracture healing remains a seriously unmet medical need affecting hundreds of thousands of patients worldwide. Despite the pandemic and subsequent seriously geopolitical and economic global events, Bone Therapeutics still remains on target for delivery of topline results for its Phase IIb study of its allogeneic cell therapy product, ALLOB, in patients with difficult tibial fractures, said Miguel Forte, MD, PhD, CEO of Bone Therapeutics. We believe ALLOB could provide difficult tibial fracture patients a convenient treatment option with a potentially superior outcome. Having successfully completed two clinical studies showing promising safety profile and efficacy signals in more than 60 patients, we firmly believe that ALLOB has the highest potential of near-term value creation and is focused on completing the current Phase IIb study. In addition, Bone Therapeutics has made a serious contribution for the future into the use of Induced Pluripotent Stem Cell (iPSC) derived, genetically engineered MSCs. Bone Therapeutics is continuing its efforts to establish value adding business collaborations and to strengthen its financial position.

Clinical and operational highlights (including post-period events)

In January 2021, Bone Therapeutics initiated the treatment of patients in the Phase IIb study of its allogeneic cell therapy product, ALLOB, in patients with difficult tibial fractures. Bone Therapeutics anticipates finalizing patient recruitment of this study in 2022. This recruitment finalization is subject, as across the industry, to evolution of the ongoing COVID-19 pandemic and the associated containment measures. Although early recruitment rates were very promising, the recruitment rates have temporarily slowed in subsequent months due to pandemic-related factors, such as reduced site activities due to staff availability and the number of available patients due to less occurrence of accidents. Bone Therapeutics has implemented several mitigating measures in collaboration with the involved clinical research organization to improve and facilitate recruitment. These measures include site expansion, training, information, best practices sharing and close monitoring of progress. As a result of these measures and the improving recruitment rate, Bone Therapeutics continues to currently expect the release of topline data by Q1 2023.

In January 2021, Bone Therapeutics signed an initial agreement for a process development partnership with the mesenchymal stromal cell (MSC) specialist, Rigenerand. This collaboration focused on further developing and enhancing Bone Therapeutics bone-forming platform.

In June 2021, Bone Therapeutics published the positive results of its Phase I/IIa clinical trial with ALLOB in patients with delayed union fractures. The results were published in Stem Cell Research & Therapy, the international peer-reviewed journal focusing on translational research in stem cell therapies. ALLOB was generally well-tolerated and that all patients met the primary endpoint.

In August 2021, Bone Therapeutics announced topline results from the Phase III knee osteoarthritis study with its enhanced viscosupplement JTA-004, its legacy non-MSC product. JTA-004 had a favorable safety profile. However, the study did not meet the primary and key secondary endpoints. No statistically significant difference in pain reduction could be observed between the treatment, placebo and comparator groups, with all treatment arms showing similar efficacy.

In September 2021, Bone Therapeutics signed a research evaluation agreement with Implant Therapeutics, the developer of hypoimmunogenic and safe harbor engineered IPSC derived cells. The agreement enables Bone Therapeutics to access, evaluate and materially transfer Implant Therapeutics Induced Pluripotent Stem Cell (iPSC) derived, genetically engineered MSCs, including lines, media, differentiation protocols and expertise.

In November 2021, Bone Therapeutics signed a non-binding term sheet for the global rights for ALLOB, Bone Therapeutics allogeneic osteoblastic cell therapy product, with one of its current Chinese partners, Link Health Pharma Co., Ltd (Link Health). The negotiations for the global rights agreement are still ongoing but take longer than expected. The envisaged completion of a final binding agreement has been delayed and is now contemplated over the course of Q2 2022.

Corporate highlights (including post-period events)

In March, 2021, Bone Therapeutics appointed the stem cell therapy industry veteran, Anthony Ting, PhD, as Chief Scientific Officer. Dr. Ting is responsible for Bone Therapeutics research activities.

In July 2021, Bone Therapeutics appointed Dr. Anne Leselbaum as Chief Medical Officer. Dr. Leselbaum brings three decades of experience in strategic international clinical development, clinical operations and medical affairs. As CMO, she takes responsibility for the leadership of all clinical development and medical affairs strategies and activities across the entire Bone Therapeutics pipeline and will oversee the regulatory interactions.

In September 2021, Bone Therapeutics appointed Lieve Creten, as interim Chief Financial Officer (CFO), succeeding Jean-Luc Vandebroek. Lieves extensive financial experience ensures the continued optimal financial control, oversight and compliance.

In October 2021, Bone Therapeutics appointed key experts to its Scientific Advisory Board (SAB). The members of the SAB consist of world-recognized scientists and clinicians in the cell and gene therapy field.

In March 2022, Bone Therapeutics announced it was redefining its strategic priorities to concentrate specifically on the development of its most advanced clinical asset, ALLOB. As a result, Bone Therapeutics will focus its R&D activities to support the clinical development of ALLOB and all activities related to the development of the pre-clinical iMSCg platform as well as all other non ALLOB related activities, were stopped. In this context, some members of Bone Therapeutics' management team will depart Bone Therapeutics in the following months in alignment with the refocus in activity. This includes Miguel Forte (CEO), Tony Ting (CSO), Stefanos Theoharis (CBO) and Lieve Creten (CFO). During the transition, CEO, Miguel Forte, will remain in function. The Scientific Advisory Board was also dissolved.

Financial highlights (including post-period events)

In July 2021, Bone Therapeutics secured a loan agreement of up to 16.0 million with the European Investment Bank (EIB). The EIB loan financing will be disbursed in two tranches of 8.0 million each, subject to conditions precedent. Following the approval of the issuance of associated warrants by Bone Therapeutics General Meetings at the end of August 2021, Bone Therapeutics received a payment from the EIB for the first tranche of 8.0 million and the EIB was granted 800,000 warrants approved by the Extraordinary General Meeting.

In August 2021, Bone Therapeutics also renegotiated 800 convertible bonds issued on May 7, 2020 (for an amount of 2 million) to Patronale Life into a loan subject to the same repayment terms as the agreement with the EIB, with the issuance of 200,000 additional warrants approved by the Extraordinary General Meeting.

In December 2021, Bone Therapeutics raised additional 3.3 million funding through a private placement with current and new institutional investors to advance its lead orthopedic asset, ALLOB, through mid-stage clinical development.

The total revenues and operating income for 2021 amounted to 2.7 million compared to 3.7 million in 2020. As a result of the reduced clinical activities following the completion of the Phase III JTA-004 study, and the slower pace of patient enrollment for the ALLOB TF2 Phase IIb study due to the COVID-19 pandemic, operating loss for the period decreased to 12.0 million from 15.0 million for the full year 2020. Consequently, cash used for operating activities amounted to 12.8 million for the full year 2021. Year-end cash position amount to 9.5 million compared to 14.7 million year-end 2020.

In April 2022, Bone Therapeutics signed a binding term sheet for a 5 million convertible bonds (CBs) facility arranged by ABO Securities. The proceeds of the financing will be used to advance the clinical development of Bone Therapeutics lead asset, the allogeneic bone cell therapy, ALLOB. ABO Securities, on behalf of the CB investor, commits to subscribe to up to 5 million in CBs. Subject to the fulfillment of condition precedents, Bone Therapeutics and ABO Securities aim to agree on and execute the final subscription agreement for the CBs and to issue the first tranche of CBs by the beginning of May 2022.

Outlook for the remainder of 2022

In the ongoing Phase IIb ALLOB clinical study in difficult tibial fractures, Bone Therapeutics clinical team, in partnership with its clinical research organization, is continuing to institute measures to mitigate the impact of the pandemic and will closely monitor the recruitment progress. As a result of the initial mitigation actions and the improving recruitment rate due to the gradual lifting of COVID-19 related measures in Europe, Bone Therapeutics expects to report topline results as scheduled by the first quarter of 2023. However, a delay cannot be excluded. Should the pandemic continue to have impact on patient availability, Bone Therapeutics may have to re-evaluate this timeline and, in that eventuality, will communicate again to the market.

The negotiations for ALLOB, with one of Bone Therapeutics current Chinese partners, for the global rights agreement are still ongoing but are taking longer than originally anticipated. The potential completion of a final binding agreement has been delayed into Q2 2022.

Subsequent to some preliminary contacts, the board of directors of Bone Therapeutics is currently examining various opportunities to combine certain activities within Bone Therapeutics, taking into account the interests of its shareholders and other stakeholders. Further announcements will be made in due course, if and when circumstances so allow or require.

Following the restructuring of the management team announced on 12 April 2022, Bone Therapeutics has initiated the search for a new CEO and CFO.

Disciplined cost and cash management will remain a key priority. The operating cash burn for the full year 2022 is expected to be in the range of 8-10 million, assuming normal operations as the effect of the ongoing COVID-19 epidemic cannot be excluded. The situation will be actively and closely monitored. The company anticipates having sufficient cash to carry out its business objectives into Q1 2023, assuming, amongst other, full issuance of the new convertible bond facility. Bone Therapeutics refers to the going concern statement in the Annual Report 2021 for all key assumptions taken.

Conference call

Miguel Forte, MD, PhD, Chief Executive Officer will host a webcast with conference call today at 3:00 pm CEST / 9:00am EST. To participate in webcast or the conference call, please use the following link:

https://us06web.zoom.us/j/81633950602

Or select your dial-in number from the list below quoting the conference ID 816 3395 0602#:

Belgium: +32 2 290 9360France: +33 1 7095 0103United Kingdom: +44 208 080 6592United States: +1 646 876 9923

The presentation will be made available on the Investors section - Presentations of the Bone Therapeutics website shortly prior to the call.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and other diseases. Currently Bone Therapeutics is concentrating specifically on the development of its most advanced clinical asset, the allogeneic cell therapy platform, ALLOB.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell and gene therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Its leading investigational medicinal product, ALLOB, represents a unique, proprietary approach to bone regeneration, which turns undifferentiated stromal cells from healthy donors into bone-forming cells. These cells are produced via the Bone Therapeutics scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, the Company has initiated patient recruitment for the Phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB continues to be evaluated for other orthopedic indications including spinal fusion, osteotomy, maxillofacial and dental.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the Louvain-la-Neuve Science Park in Mont-Saint-Guibert, Belgium. Further information is available at http://www.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerLieve Creten, Chief Financial Officer ad interimTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicBert BouserieTel: +32 (0)488 40 44 77bert.bouserie@bepublicgroup.be

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: +33 (0)1 44 71 94 94bone@newcap.eu

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

Excerpt from:
Bone Therapeutics announces 2021 full year results - GlobeNewswire

Bone Marrow Stem Cells Comments Off on Bone Therapeutics announces 2021 full year results – GlobeNewswire | April 29th, 2022

Early outcomes with the combination of JSP191, fludarabine, and low-dose total body radiation (TBI) demonstrated facilitation of full donor myeloid chimerism, clearing of minimal residual disease (MRD), and a well-tolerated safety profile in older patients with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) receiving non-myeloablative (NMA) allogenic hematopoietic cell transplantation (AHCT).

Results from the phase 1 trial (NCT04429191) presented at the 2022 Transplantation & Cellular Therapy Meetings, showed there were no infusion toxicities or serious adverse events with JSP191, and no instances of primary graft failure in first 24 patients enrolled on the trial; only 1 patient had secondary graft failure and went on to have successful retransplant. Additionally, MRD clearance was observed in 12 patients, and JSP191 pharmacokinetics were shown to be predictable.

AHCT is the only curative treatment for many patients with MDS/AML, even though there have been advancements in therapy for these patients in recent years. While transplant has proven feasible for adults well into their 70s, the optimal conditioning regimen for older adults remains unknown as more intensive regimens tend to be associated with transplant-related mortality, while less intensive nonmyeloablative regimens have resulted historically in higher rates of disease relapse and progression, Lori Muffly, MD, MS, said in her presentation.

Therefore, a conditioning regimen that results in minimal toxicity but has enhanced disease control is needed in order to improve transplantation outcomes in this population, Muffly, associate professor of medicine (blood and marrow transplantation and cellular therapy) at Stanford Healthcare, continued.

JSP191 is a humanized monoclonal antibody meant to block stem cell factor binding site on CD117, which is necessary for hematopoietic stem cell (HSC) survival and HSC interactions in the bone marrow niche. After the bone marrow niche is emptied because of JSP191 binding to CD117, healthy donor cells are able to engraft. Preclinical models showed synergy between anti-CD117 monoclonal antibodies and low-dose TBI to help deplete HSC and facilitate donor cell engraftment.

For the first 24 patients with MDS (n = 13) or AML (n = 11), primary end points evaluated were safety, tolerability, and pharmacokinetics of the combination. Secondary end points included engraftment and donor chimerism, MRD clearance, relapse-free survival, graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Patients received AHCT, then 200 to 300 cGy of TBI, 30 mg/m2 of fludarabine for 3 days, and 0.6 mg/kg of intravenous JSP191.

To determine the starting date of fludarabine, real-time pharmacokinetic measurements and modeling were used after JSP191 was administered. For the first 7 patients, TBI was increased from 200 to 300 cGy to aid lymphoablation. Tacrolimus, sirolimus, and mycohphenolate motefil were used as GVHD prophylaxis.

Consistent pharmacokinetics and predictable clearance were observed with JSP191 over the 2 weeks after administration. All patients were able to receive donor cell infusion between 9 and 15 days following administration of the antibody. Interestingly, we did see in some patients very low levels of the antibody present on the day of donor cell infusion, and this did not appear to impact donor cell engraftment, Muffly said.

Bone marrow aspirations taken at screening and between administration of the antibody and fludarabine/TBI showed JSP191 depletes hemopoietic stem and progenitor cells (HSPC). In the CD34-positive, CD45RA-negative population, there was a 66% mean depletion of HSPC. The investigators do not believe this reflects the nadir of HSPC depletion, Muffly explained, and that the depletion continues until donor stem cell infusion.

All patients experienced neutropenia followed by neutrophil engraftment between TD+15 and TD+26. Primary engraftment was seen in all patients, with only 1 patient losing myeloid chimerism early, which was associated with disease progression. T cell chimerism improved when patients went up from 200 to 300 cGy.

Using flow cytometry, cytogenetics, and next-generation sequencing, investigators were able to track MRD in patients with de novo AML (n = 8) and AML from MDS (n = 3). Of the 9 patients with AML who were MRD positive at the time of enrollment, 6 were MRD negative at the time of follow-up. Eleven of 13 patients with MDS were MRD positive at enrollment, and 8 were MRD negative at the last follow-up.

After 6 months median follow-up (range, 2-12 months), there were no reports of classical grade II-IV acute GVHD. One case of late onset grade III-IV acute gastrointestinal GVHD was reported as of the latest follow-up, but this patient had non-relapse mortality. Any instances of chronic GVHD has yet to be reported due to insufficient median follow-up time. Morphologic relapse occurred in 4 patients, 3 with AML and 1 with MDS.

The median age for these patients was 70 years (range, 62-79), with a requirement of 60 years of age or older or an AHCT-comorbidity index of 3 or more to enroll in the trial. They could not have prior AHCT and needed a human leukocyte antigenmatched related or unrelated donor. Over half of patients received only a hypomethylating agent-containing regimens.

JSP191 in combination with fludarabine and low-dose TBI is a novel conditioning platform that appears safe, well tolerated, has demonstrated on-target effects of HSPC depletion, permits full donor myeloid chimerism, and results in promising early MRD clearance, Muffly concluded.

Reference:

Muffly L, Lee CJ, Gandhi A, et al. Preliminary data from a phase 1 study of JSP191, an anti-CD117 monoclonal antibody, in combination with low dose irradiation and fludarabine conditioning is well-tolerated, facilitates chimerism and clearance of minimal residual disease in older adults with MDS/AML undergoing allogeneic HCT. Presented at: 2022 Transplantation & Cellular Therapy Meetings; Salt Lake City, UT; April 23-26, 2022. Abstract LBA4. https://bit.ly/3xRTwee

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Interim Data Targeting CD117 Show Promising MRD Results and Safety in MDS/AML - Targeted Oncology

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Hairy cell leukemia is a rare type of blood cancer that can affect adults. In people who receive treatment, the long-term outlook for hairy cell leukemia is good.

Hairy cell leukemia (HCL) occurs when bone marrow produces too many white blood cells called lymphocytes.

The disease gets its name from the hairlike projections on its cells. HCL cells can affect the bone marrow, spleen, liver, and lymph nodes.

According to the National Organization for Rare Disorders, HCL is more common in males over the age of 50 years.

HCL affects roughly 6,000 people in the United States, with around 600800 new diagnoses each year. Around 12% of all adult leukemias are HCL.

In many cases, the long-term outlook for HCL is good, with people often continuing to live good-quality lives for years with medical care.

In this article, we look at the outlook and survival rates for HCL, the risk of secondary cancers, and treatment options.

Learn about the symptoms of HCL here.

HCL is a chronic disease, and although there is no cure for it, the condition is treatable. Treatment is usually highly effective and can help people continue to live normal lives.

According to the National Cancer Institute, HCL progresses slowly or does not worsen at all.

The Leukemia and Lymphoma Society reports that the 5-year event-free survival rate for HCL is 90% in people who received initial treatment with the chemotherapy drug cladribine. This means 90% of people will still be alive 5 years after diagnosis.

Treatment with cladribine has led to roughly 85% complete remission and around 10% partial response in people with HCL.

A 2020 study looked at survival rates in 279 people diagnosed with HCL between 1980 and 2011. The median age of the participants was 59 years old. In 208 of the participants, the first-line treatments were the drugs cladribine or pentostatin.

A 10-year follow-up found that the median survival rate was 27 years overall, with 11 years of relapse-free survival. There was a relapse rate of 39%. The study concluded that people with HCL have a good long-term outlook.

Research suggests that there may be racial disparities in HCL outcomes. A 2015 study included participants of the following racial groups:

The study found that the 10-year survival rate was worse in African American participants than in those of other racial groups.

Half of African American participants were alive at the 10-year follow-up, whereas more than two-thirds of those in other racial groups were alive at the follow-up.

The researchers concluded that the biological, socioeconomic, and health system factors contributing to this disparity need further investigation.

According to a 2020 study, people with HCL have an increased risk of secondary cancer.

Among 279 participants, 59 people developed at least one secondary cancer. The most common secondary cancers were prostate cancer, nonmelanoma skin cancer, and blood cancers.

The study did not find that treatment with purine analogs, such as cladribine or pentostatin, was a risk factor for secondary cancers.

However, according to the National Cancer Institute, cladribine and pentostatin may increase the risk of Hodgkin lymphoma and non-Hodgkin lymphoma.

Some research suggests that HCL and its effects on the body may increase the risk of secondary cancer.

People with HCL must attend regular cancer screenings to detect any early signs of secondary cancer.

Blood cell changes in those with HCL may result in compromised immune systems, making people more susceptible to infection or autoimmune disease.

HCL responds very well to treatment, which aims to manage the cancer rather than cure it.

Unlike with many other types of cancer, doctors may choose to wait before starting treatment.

Doctors will monitor the condition and may only begin treatment if they believe it is necessary to control it. This can help avoid any unnecessary side effects of treatment.

The type of treatment will depend on each condition but may include the following:

Cladribine and pentostatin are purine analogs, which are the first-line treatment for HCL.

According to the Hairy Cell Leukemia Foundation, both medications are highly effective treatments and can result in long-term remission.

In 2018, the Food and Drug Administration (FDA) approved another drug, moxetumomab pasudotox, to treat HCL. Doctors may use this drug in people who have not responded to standard therapies.

Interferon is a drug that doctors may use to treat HCL. Interferon uses the bodys immune system to help fight off cancer. Interferon affects how cancer cells divide and helps slow tumor growth.

Doctors may also use a biologic drug called rituximab, known by the brand name Rituxan, if people with HCL have not responded to other treatments. Rituximab is an antibody that attaches to HCL cells. Doctors may also use rituximab in combination with chemotherapy as a first-line treatment.

Targeted therapies use medications or other substances to find and destroy cancer cells. Targeted therapies may cause less harm to healthy cells than other treatments, such as radiation therapy or chemotherapy.

One type of targeted therapy to treat HCL is monoclonal antibody therapy. A laboratory creates antibodies that attach to cancer cells and destroy them or prevent them from growing and spreading. The biologic drug rituximab is an example of a monoclonal antibody.

Splenectomy is a surgical procedure to remove the spleen. This may be necessary if HCL causes an enlarged spleen.

However, doctors rarely perform splenectomy for HCL because there are medications that can effectively reduce the size of the spleen.

Learn more about immunotherapy for leukemia here.

Treatments for HCL can have the following side effects:

Cancer treatments may also cause other side effects, such as fatigue, appetite loss, or nausea.

Before starting treatment, people can discuss any potential side effects and the risks and benefits of each treatment option with their healthcare team.

Learn more about side effects here.

HCL is a rare type of leukemia. Other types of leukemia include:

HCL is a rare type of adult leukemia. It is more common in males over the age of 50 years.

The overall outlook for people with HCL is good. Treatment with chemotherapy drugs, such as cladribine and pentostatin, is highly effective and may result in long-term remission.

Treatments for HCL may have side effects. People can discuss any treatments potential risks and benefits with their healthcare team.

More here:
Hairy cell leukemia: Outlook, treatment, and what to expect - Medical News Today

Bone Marrow Stem Cells Comments Off on Hairy cell leukemia: Outlook, treatment, and what to expect – Medical News Today | April 29th, 2022

Abstract: Glucose metabolism has been the focus of research in order to understand pathological conditions associated with diseases such as neonatal hypoxic-ischemic-encephalopathy (HIE), cerebral palsy (CP) and cerebral infarction.

Objective:To evaluate the use of molecular imaging (SPECT and PET) for children with HIE and CP before and after cell therapy, and to propose future perspectives on the use of those modalities for assessment of brain function in children with these conditions.

Methods:PubMed search for studies using PET or SPECT scans for HIE and CP in children.

Results:We identified 18 PET and 17 SPECT studies that have been performed in cases under age of 19 over the past three decades (19912021). Six papers on PET use consisted of one with human umbilical cord derived mesenchymal stromal cells, one mobilized peripheral blood mononuclear cells, three autologous bone marrow mononuclear cells and one allogeneic umbilical cord blood. 4/6 papers reported that PET-CT scan revealed increased glucose metabolism and 1/6 showed no significant change in glucose metabolism after cell therapy. One article on SPECT reported that 2/5 cases had improvement of cerebral perfusion in the thalamus after treatment.

Discussion:SPECT in the first few weeks of life is useful and more sensitive than MRI in predicting major neurological disability. SPECT is not appropriate for neonates because of the risk of radiation, improvement of other clinical test equipment. PET studies reported high glucose metabolism in the early neonatal periods in children with mild to moderate HIE, but not in the most severe cases, including those neonates that died.We suggested that PET could be more useful tool to estimate effectiveness of stem cell therapy than SPECT.

Conclusion:PET might be a good clinical modalities to clarify mechanism of stem cell therapy for CP. We need further clinical studies to clarify more precisely.

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Molecular Imaging (PET and SPECT) for Children with Hypoxic-ischemic-encephalopathy and Cerebral Palsy before and after cell therapy - Newswise

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Abstract

Arrhythmias are a major cardiac complication reported among patients with multiple myeloma (MM), but these have not been further characterized in this population. We explored the prevalence of arrhythmias and examined the predictors of mortality among patients with MM with arrhythmias. The National Inpatient Sample data collected between 2016 and 2018 were used to conduct retrospective analyses. Multivariable logistic regression analyses were done to examine the predictors of mortality among patients with MM with arrhythmias. 16.9% of patients with MM reported a diagnosis of any arrhythmias and 70.7% of these were atrial fibrillation. Patients aged 70 years and above had 21% lower odds (adjusted OR (AOR): 0.79; 95% CI: 0.68 to 0.92) of inpatient mortality relative to younger patients. Those in the non-Hispanic black, Hispanic, and non-Hispanic other category were 1.38 (95% CI: 1.16 to 1.64), 1.53 (95% CI: 1.19 to 1.97), and 1.69 (95% CI: 1.29 to 2.21) times more likely to die during hospitalization compared with their counterparts who were non-Hispanic whites. Relative to patients with MM who were on Medicare, those on private (AOR: 1.28; 95% CI: 1.06 to 1.54) and other insurance types (AOR: 1.78; 95% CI: 1.23 to 2.58) had higher odds of mortality. Other predictors of inpatient mortality were elective admission (AOR: 0.67; 95% CI: 0.52 to 0.85) and Charlson comorbidity indices between 57 (AOR: 1.23; 95% CI: 1.07 to 1.41) and 8 (AOR: 1.45; 95% CI: 1.21 to 1.73) compared with comorbidity indices between 0 and 4. Our study adds to the body of knowledge on the need for proper diagnosis and management of cardiac arrhythmias in patients with MM. Research is needed to further assess the time of arrhythmia diagnosis and its impact on health outcomes among patients with MM.

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Burden of arrhythmias and predictors of mortality among multiple myeloma patients with arrhythmias - Journal of Investigative Medicine

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Stem cell transplants can effectively cure a wide range of diseases, from blood cancers to rare genetic disorders. They've been used for decades and are considered standard treatment for certain conditions.

But for a good number of patients, stem cell transplants are out of reach. Drug regimens used to prepare the body for a transplant are toxic and can cause serious side effects. The transplanted cells don't always "engraft," or take root in the bone marrow. Even when they do, patients' disease may linger or recur.

A biotech startup launching Wednesday with $50 million in funding hopes that, by combining cell, antibody and gene editing technologies, at least some of these problems can be overcome. Called Cimeio Therapeutics, the new company is led by a team of pharmaceutical industry veterans and an advisory board filled with scientific luminaries, including immunologist Jeffrey Bluestone and gene editing pioneer Fyodor Urnov.

Cimeio's approach involves "shielding" transplanted cells by genetically editing them in ways that allows paired immunotherapies to be safely used both before and after a transplant.

Thomas Fuchs

Courtesy of Cimeio Therapeutics

"We think that this can really unleash the power of hematopoietic stem cell transplant and make a lot more patients eligible for it," said Thomas Fuchs, Cimeio's CEO and a former Genentech executive.

The "shielding" technology used by Cimeio was developed in Switzerland at the laboratory of Lukas Jeker, a physician-scientist from Basel University Hospital who will join Cimeio as head of gene editing.

Jeker's lab discovered that protein receptors on the surface of cells could be genetically edited in such a way that prevented antibodies from binding to them, while leaving their function intact. In preclinical testing, these edits could cloak, or "shield," the cells from being depleted by antibody drugs and T cell therapies.

The work could have powerful implications for improving stem cell transplant and adoptive cell therapy, according to Fuchs.

Once a stem cell or T cell is shielded, a complementary immunotherapy could be used to either help ready patients for a transplant or to further treat disease afterwards, he said. "Maybe you could give a cycle or two of the paired immunotherapy, implant the shielded cells and then continue to administer the immunotherapy," he added.

If the shielding works as intended, Cimeio could develop treatments for conditioning that are more tolerable than the chemotherapy or radiation-based regimens currently in use. Shielding might also allow existing drugs that target cell proteins on healthy as well as diseased cells to be used more flexibly with transplants, such as to treat residual disease that lingers afterwards.

For example, Cimeio could engineer stem cells that are protected against binding via a protein called CD19 that's often the target for CAR-T therapies that treat lymphoma, but is also found on healthy B cells that help the immune system fight off threats.

"One benefit could be that you could prevent a lifetime of B cell depletion, which happens when you give a CAR-T," said Fuchs.

Alex Mayweg

Courtesy of Cimeio Therapeutics

Cimeio was built from Jeker's lab by Versant Ventures at the company's "Ridgeline" incubator in Basel, which has previously produced companies like Monte Rosa Therapeutics and Black Diamond Therapeutics. The initial $50 million Versant provided will fund Cimeio through next year, said Alex Mayweg, a managing director at the venture firm and a Cimeio board member. Additional investors will be brought on later this year or early next, Mayweg said.

Cimeio will need the money, as its research and development plans are expansive. The company has identified four drug candidates already and envisions a dozen more behind those, said Fuchs. Its research spans blood cancers, rare genetic diseases and autoimmune disorders.

In some cases, Cimeio will develop paired immunotherapies to go with the shielded cells. In others, it will use existing treatments. Three of the first four candidates involve protecting hematopoietic stem cells, while the fourth involves T cells. The company hopes to begin human testing next year.

Cimeio plans to choose gene editing technologies based on the type of alteration it needs to make to shield cells. "Rather than building up an internal editing capability," Mayweg said, "we wanted to stay as flexible as possible."

That might mean partnerships or alliances with other companies, some of which have reached out to Cimeio already, according to Mayweg.

Cimeio is aided by a group of scientific advisers notable for their work in areas the company is focusing on. Urnov, of the University of California, Berkeley, is well known for his research in gene editing using zinc finger nucleases and CRISPR. Bluestone previously led the Parker Institute for Cancer Immunotherapy and is CEO of the cell therapy-focused biotech Sonoma Biotherapeutics.

Suneet Agarwal, a co-program leader of the stem cell transplant center at Boston Children's Cancer and Blood Disorders Center, is also on the advisory board, while Cimeio has a research collaboration in place with Matthew Porteus, a gene editing specialist at Stanford University.

About 20 people currently work at Cimeio directly, a number Fuchs expects will grow as the company's research advances. Another 15 are currently supporting Cimeio from Versant's Ridgeline group.

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Versant-backed startup launches with plans to broaden cell therapy's reach - BioPharma Dive

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ABC24 talked with Randy Hutchinson from the Better Business Bureau of the Mid-South about a lawsuit against one company and what consumers need to watch out for.

MEMPHIS, Tenn. The Federal Trade Commission and Georgia Attorney General have sued the founders of a company they claim has made unsubstantiated claims its stem cell therapy can treat arthritis, joint pain, and other orthopedic ailments.

The company is called Stem Cell Institute of America. It claimed its treatments are comparable to or better than surgery, steroid injections, and painkillers. The FTC said the company charged up to $5,000 per injection. It said a related company taught chiropractors and other healthcare professionals how to offer stem cell therapy.

ABC24 talked with Randy Hutchinson from the Better Business Bureau of the Mid-South about the claims and what consumers need to watch out for.

So what are the facts about stem cells?

They're sometimes called the body's "master cells" because they develop into blood, brain, bones, and other organs.

Stem cells from bone marrow or blood are used to treat certain kinds of cancer and disorders of the blood and immune system. But other uses have not been properly studied and approved.

The FDA cites these potential risks from unproven treatments:

There could be safety risks even using a persons own stem cells.

Other claims by some companies

The FTC has also looked into companies claiming their stem cell therapies can treat Parkinson's, multiple sclerosis, COVID, and a host of other ailments. They're sometimes referred to as "regenerative medicine."

So what do consumers need to do?

Take miracle health care claims with a grain of salt.

Check out a company and treatment online using terms like "complaints," "scam" and "reviews."

Consult your own health care provider before using any product or treatment.

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Be wary of companies offering stem cell therapy for arthritis, joint pain, COVID, and more. Heres why - WATN - Local 24

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Marc Howard was diagnosed with multiple myeloma. He will receive a transplant using his own cells later this year.

COLUMBUS, Ohio It all started with back pain that seemed to be progressively getting worse.

My back, the structure of my body, was like starting to deteriorate, and I could tell, he said. I'm tall, so when I started to lean over, and the pain and things of that nature, I'm like, yo, something's going on.

His longtime love Sonia Grant noticed, too. And she was right there to encourage him to get it checked.

When he did, doctors found holes in his spine where his bone had deteriorated. He had a vertebroplasty procedure to have those holes filled with bone cement. But that was not the end of his journey. In fact, it was really only the beginning.

After the surgery, he was okay for about a month, then I saw him (leaning) over again, and he couldnt get off the bed one day, Grant said. I said, uh uh, were going back up there (to the hospital). Theres something wrong.

And something was. Howard was diagnosed with multiple myeloma, a cancer that forms in the plasma cells.

I dont want to be the woe is me, Howard said. I want to be the success story for somebody, for the world to look at, like, that man went through a situation, and he made it.

And hes making it so far, with the help of Grant. Hes been doing weekly chemotherapy treatments and taking daily medication. Meanwhile, Grant is making sure hes eating his fruits and veggies and drinking plenty of water, too.

If youre not up to the challenge, I will help you get there, I will, Grant said. Because failure is just not a thing when it comes to fighting something like cancer. You gotta fight, you just gotta fight.

This fight will culminate with a major procedure later this fall via OhioHealths new Blood and Marrow Transplant Program. Howard will be one of the first patients to receive an autologous stem cell transplant, meaning the procedure will use his own cells.

Dr. Yvonne Efebera, the medical director for the program, explains this process is different than a procedure using donor cells.

BMT, blood and marrow transplant, is a process where, certain diseases require this, where non-functioning, deficient bone marrow or cancer cells are eliminated by giving high-dose chemotherapy, with or without radiation, and then replaced by new, healthy cells, Dr. Efebera said.

Shes been treating Howard throughout this process and points out that this is one of the benefits of the new program. Before, patients who needed transplants would have to be sent to other healthcare systems. Now, they can go from start to finish with the same clinical team.

Marc always wanted to be the first, she joked. Hes anxious to have his stem cells to be the first collected and the first admitted.

Both Howard and Grant are up to the challenge.

Its a battle, Grant said. Were halfway through the battle, and so, were going to get all the way to the end of the battle. Bruised, not broken. But were in the battle. But were going to get through it.

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Columbus man to be one of first to receive transplant via new OhioHealth program - 10TV

Bone Marrow Stem Cells Comments Off on Columbus man to be one of first to receive transplant via new OhioHealth program – 10TV | April 15th, 2022

Investigators uncovered potential mechanisms of resistance to CD19-directed CAR T-cell therapy in patients with pediatric acute lymphoblastic leukemia.

Bone marrow samples from a trial examining CD19-directed CAR T-cell therapy helped investigators identify epigenetic biomarkers predicting resistance to therapy in pediatric acute lymphoblastic leukemia (ALL), according to a presentation from the 2022 American Association for Cancer Research (AACR) Annual Meeting.1

Investigators observed 3 key features of leukemia cells that do not respond to CAR T-cell therapy: hypermethylation of DNA, a stem cell-like phenotype and inherent plasticity, and decreased antigen presentation. These are independent of CD19 status and leukemia subtype, indicating a new predictive biomarker.

Whats most important about this is we can detect it prior to therapy in patient samples, so this highlights its potential as a biomarker for response, Katherine E. Masih, BS, an NIH-Cambridge scholar in the Genetics Branch, Center for Cancer Research at the National Cancer Institute, said in a press conference. We hope that eventually this can improve patient selection and eligibility for CD19 CAR T-cell therapy.

CD19 is a common target of CAR T cells, and resistance to treatment can occur even if patients continue to show CD19 expression. The investigators explored primary non-response (PNR) to CAR T-cell therapy, which occurs in 10% to 20% of patients and whose causes are not fully understood. Known reasons for non-response to CAR T cells include collection of dysfunctional T cells and decreased death cell receptors on the cell surface.2,3

The investigators used bone marrow samples from 14 participants in the PLAT-02 trial (NCT02028455) of CD19-directed CAR T-cell therapy for relapsed/refractory pediatric ALL.1 These samples included those of 7 patients who had a complete response to therapy and 7 who had no response. Non-response was defined as not achieving and maintaining minimal residual disease negativity at 63 days.

A multiomic analysis of the bone marrow included whole-exome sequencing, RNA sequencing of the bulk cells, single-cell RNA sequencing, array-based methylation analysis, and ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing).

In patients who went on to have PNR, investigators discovered epigenetic markers including 238 regions of hypermethylated DNA, which is associated with inactivated genes (P = 8.15 10-25). These regions are known to be activated in stem cells.

The ATAC-seq analysis showed increased accessibility of chromatin at regions linked to stem cell proliferation (normalized enrichment score [NES] = 2.31; P < .0001) and cell cycling (NES = 2.27; P < .0001), indicating inherent plasticity that may allow leukemia cells to adapt to resist CAR T-cell therapy.

Investigators found that the epigenetic differences did not lead to differences in phenotype of B cells between primary sensitive and PNR patients. However, PNR cells did show an increase in regions associated with hematopoietic stem cells and myeloid and lymphoid progenitors. In addition, investigators observed decreased antigen presentation and processing that could lead to lack of response in cells that still express CD19 (P = .0001).

These factors characterized a potential novel biomarker associated with PNR that investigators named Stem-Cell Epigenome with Multi-Lineage Potential (SCE-MLP). Masih acknowledged that the sample size of 14 patients was small and more research on SCE-MLPs link to PNR is needed. We would love to see this validated in a larger cohort with more cases of PNR that exist around the country, she said.

Another potential use of SCE-MLP could be to find ways to overcome resistance to CAR T-cell therapy by combining it with targeted therapies that disrupt these epigenetic factors for resistance.

Currently, the investigators hope that this research will be used to shape patient selection for CAR T-cell therapy and alternative therapies.

If we can reliably identify responders, perhaps through screening for SCE-MLP, we can prioritize less toxic targeted therapies for our patients and overall improve outcomes for children with this devastating disease, Masih said.

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Molecular Characteristics of Resistance to CD19-Directed CAR T Cells Revealed in Pediatric ALL - Cancer Network

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Photo: Contributed

Salny Ehman, left, and Tom Ellison, the man whose life she saved through a bone marrow donation.

Penticton resident Salny Ehman saved a complete stranger's life, and hopes to inspire others to do the same.

Ehman, now 35, signed up to be a bone marrow donor at the age of 19, after watching her grandmother's sibling go through leukemia.

"She has a whole bunch of siblings, and one of them had blood cancer, and only she was a match. And the math of that blew me away, how likely is it to have a close relative that can help?" Ehman said.

"If it's that unlikely to have a match when you have that many siblings, then people need to sign up."

Ehman did just that. She registered with Canadian Blood Services, and a few months later, got a call that she was a match with an anonymous recipient signed up through an American service, fighting cancer and in need of bone marrow stem cells.

Despite not knowing who she was donating to, Ehman underwent the donation procedure, and then one year later, did the same thing again after learning the recipient's body had been rejecting the donated cells.

"One year after the second donation, we were both allowed to say yes, we would like to know the other person. And we both said yes, but I was living in Nova Scotia at the time," Ehman said, having learned her stem cell recipient, Tom Allison, lived in Seattle.

"The only information given to me about [my donor] was it was a 19 year old girl from Nova Scotia. And I thought, what's a 19 year old girl doing on a bone marrow registry for?" Allison said.

"Neither one of my boys were matches, and neither one of my brothers. So this seemed just a million to one chance for somebody out there with a match that's no relation to me."

Allison and Ehman ultimately got in touch and kept in touch for more than a decade.

"We would write each other letters over the years, and little postcards," Ehman said.

"And then I moved here [to Penticton] two years ago. So as soon as I moved here, I was like, 'Wow, I'm so close.' Just a quick drive, like three and a half hours away."

She and Allison, who is now in his 60s and healthy post-cancer, met up in person recently, and Ehman was thrilled to see him thriving thanks to her donation.

"Second to my daughters, [donating] was the best, best experience in my entire life. And to know that he was out there, and spending time with his family, his grandchildren, it really meant a lot. And it showed me what I was capable of," Ehman said.

She and Allison remain good friends, and she urges anyone who can help to either sign up to be a donor, or if they can't participate in that way, give financially to Canadian Blood Services.

"There's lots of opportunities to help that cause," she said.

Find out more about Canadian Blood Services and how you can help here, and learn how you can be the match that saves someone's life here.

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Penticton woman donated bone marrow to save stranger's life, urges others to do the same - Penticton News - Castanet.net

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This article was originally published here

Mol Biotechnol. 2022 Apr 9. doi: 10.1007/s12033-022-00487-z. Online ahead of print.

ABSTRACT

Exosomes-related microRNAs (miRNAs) have been considered to be the significant biomarkers contributing to the development of atrial fibrillation (AF). We observed the implicit mechanism of exosomes-miR-148a derived from bone marrow mesenchymal stem cells (BMSCs) in AF. The AF cell and mice models were established firstly. QRT-PCR and Western blot analysis were applied to detect the expression of miR-148a, SPARC-associated modular calcium-binding protein 2 (SMOC2), Bcl-2, Bax, and caspase-3. BMSCs were separated from healthy mice and exosomes were obtained from BMSCs. BMSCs were transfected with mimics and inhibitor, and HL-1 cells were treated with mimics and pcDNA3.1. MTT assay were used to detect cell viability of cells. Flow cytometric analysis and TUNEL analysis were used for detecting cell apoptosis of cells. In our study, exosomes derived from BMSCs inhibited the development of AF, and miR-148a acted a vital role in this segment. SMOC2 was a target gene of miR-148a and promoted apoptosis of HL-1 cells. Additionally, miR-148a mimics decreased cellular apoptosis, eliminated SMOC2 expression, and elevated Bcl-2 expression in AF-treated cells. Collectively, miR-148a overexpressed in BMSC-exosomes restrained cardiomyocytes apoptosis by inhibiting SMOC2.

PMID:35397056 | DOI:10.1007/s12033-022-00487-z

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microRNA-148a in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Cardiomyocyte Apoptosis in Atrial Fibrillation by Inhibiting...

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Three children are fighting for their lives and require stem cell transplants to cure their blood cancers and disorders.

Rayaan (four months), Emily (five months) and Neo (7) all share one commonality: being diagnosed with life-threatening blood diseases. They are waiting on blood stem cell transplantations from unrelated donors.

Between 800 and 1 000 children in South Africa are diagnosed with cancer annually.

However, this number does not account for the almost 50% of cases of childhood cancer that are never diagnosed, due to a lack of knowledge regarding the disease and how it presents in children.

Because children still experience growth spurts within a short space of time, this may cause blood cancer and disorders to spread quicker and more aggressively. Therefore, diseases affecting young children are those most often occurring in the developing cells, such as bone marrow, blood, kidneys and nervous system tissues.

Rayaan, Emily and Neos families lives have been turned upside down by blood cancer and disorders.

Rayaan was diagnosed with life-threatening acute myeloid leukaemia when he was just eight weeks old. AML usually requires immediate treatment and for Rayaan, bone marrow or blood stem cell transplant is his only chance of a cure.

Without a successful transplant, Rayaan will have to endure continued chemotherapy and isolation, which will expose him to the terminal effects of infection. Rayaan is now in search of an unrelated matching donor, but the low representation of diverse stem cell donors across the country and in the global registry hampers the chances of saving this courageous baby.

Arlene said watching her son endure this pain is heartbreaking and there have been some very dark days. At one point, he had to be resuscitated after a spinal lumbar puncture, but their courageous little fighter battled on and still wakes up every day with a smile on his face.

Please help my baby to live. He is just too little to suffer like this. Dont delay, you could be his perfect match, Arlene added.

Meanwhile, five-month-old Emily from Johannesburg has been battling a blood disorder following her diagnosis in November at only three months. She was diagnosed with juvenile myelomonocytic leukaemia (JMML) and is undergoing treatment, hoping a stem cell transplant will be performed soon.

As in Rayaans case, Emilys best chance at survival is a blood stem cell transplant. Dr Theo Gerdener, a clinical haematologist at Albert Alberts Stem Cell Transplant Centre and medical director at DKMS Africa, said:

JMML, which is especially prevalent in young children, is a rare cancer of the blood and occurs when white blood cells, known as monocytes and myelocytes, mature abnormally. This cancer can occur spontaneously or, sometimes, is linked to other genetic disorders.

Leukaemia affects white blood cells and bone marrow, and alarmingly, childhood leukaemia accounts for around 25% of all cancer in children. With proper diagnosis and management, including stem cell transplantation, childhood leukaemia can be cured in 85% to 90% of patients.

According to Natalie, Emilys mother, her daughter has already endured multiple blood and platelet transfusions, frequent injections and other medication, lengthy hospital stays, including isolation and ICU admission, as well as surgery to insert a port in her chest for intravenous administration.

Her parents desperately hope to find a stem cell donor match through DKMS global stem cell registry and donor centre to provide them with this one in 100 000 chance.

Were keeping positive and are hoping a match will be found for Emily. We hope she grows up, has a normal childhood and becomes a beautiful, bright young lady, said Natalie.

Neo was diagnosed with Fanconi anaemia in April 2019 at only four years old. A couple of years earlier, his older sister, who was also diagnosed with the same blood disorder, received a stem cell donor transplant, giving her a second chance at life.

Their dad, Phoebus, recalls the late-night rushes to the hospital, overnight stays and time away from work, as both parents grappled with the unusual, but persistent symptoms in their child, as Neo endured uncontrollable nosebleeds, debilitating fatigue, prominent bruising and innumerable fevers and infections owing to his compromised immune system.

Neo is transfusion-dependent and receiving steroid treatment, among other things. He is also searching for his second chance at life through an unrelated donor match to provide him with a life-saving blood stem cell transplant.

A donor with the same ethnic background as a patient may be a better match than one who comes from an entirely different background.

Globally, there are a low number of registered donors among the black, Indian and mixed-ethnic populations, meaning the pool of prospective matches is significantly lower.

For patients like Neo, a substantial increase in the registration of black donors will directly impact his chances of a successful transplant from a matched donor.

Neos family has thrown its support behind DKMS Africa to champion the cause of education and awareness around blood diseases.

Also Read:Young couple says I do with the help of generous donors

People need to be aware of these medical conditions and empower themselves with the knowledge. Some people and organisations are there to help. People should not be afraid to reach out, said Phoebus.

If you are in good health and between the ages of 18 and 55 and considering joining the registry, visit http://www.dkms-africa.org or call 0800 12 10 82, weekdays between 08:30 and 16:30.

Once you have registered online, a swab kit is sent to you via courier and then collected when you have completed the process (at no cost to you). Take action, save a life!

Also Read:Become an organ donor and help save a life

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Donors needed to save young lives - Benoni City Times

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