If you've suffered a spinal cord injury, it is only natural for you to search out the latest breakthroughs in medicine and technology to find a treatment that can get you back to the way things used to be. And one promising branch of current medical research is in the direction of stem cell therapy. But it's important to understand the scope of this relatively new science and to have realistic expectations about the outcomes.

We often get this question, in various forms, from people who suffer from spinal cord injuries:

Is stem cell therapy a cure?

Well, as of today, the sad answer is no. There is no evidence, so far, that stem cell therapy can cure a spinal cord injury. But I'd suggest that the real question they should be asking is this:

Does stem cell therapy have the ability to help after a spinal cord injury?

The answer to this question isn't that firm, but it is a lot more hopeful than the other question. The answer is maybe, sometimes, and we don't know. The reason for this ambiguity is that stem cell therapy for spinal cord injuries is in its infancy as a treatment. In fact, as of January of 2020, the FDA hasn't approved any stem cell therapies for this purpose. So, these treatments are not available in the mainstream medical market. The U.S. Food and Drug Administration has even expressed concerns that patients seeking cures and remedies are vulnerable to stem cell treatments that are currently illegal and potentially harmful.

So, the good news is that there have been some newsworthy and amazing stories of recoveries after stem cell treatments. The unfortunate news is that you won't be able to get stem cell treatment for your SCI through traditional hospital care.

While commercially available stem cell therapies are not available, there are plenty of existing clinical trials out there for which you might qualify. And, a lot of progress is being made in this area. These ongoing trials are being held at various locations around the United States.

Some of these trials focus on individuals who are in the acute stage of their SCI. That generally means they are patients still within 72 hours of the initial injury. Given the short time range on these tests, it is not generally possible to volunteer for them. Rather, the doctors administering the clinical trials will generally seek out patients in the hospital as participants.

There are other trials, however, that are researching the effects of stem cell therapy on patients months or even years after an injury. These are the kinds of trials that patients can apply for and have any real hope of participating.

So, the main point is that, when you're researching trials, it's very important to consider the qualifications. If you don't meet the criterea, you're wasting your time.

With that in mind, if you've decided to pursue clinical trials as a source of treatment, there are a couple of really great resources that can help you to find the right study for you. There are two websites that you can use. They are scitrials.org and clinicaltrials.gov.

This website can really help you to narrow down the search when you're looking for different experimental therapies that could be helpful for your treatment. On the site, you can search for trials based on geographic location, the level of injury, the age of the injury, and you can even use a keyword search.

This is a much larger website, and a much larger resource. And, it's run by the government. It is definitely worth reviewing, especially if you couldn't find what you were looking for at scitrials.org. On the downside, the sheer breadth of information can be overwhelming. Clinicaltrials.gov lists virtually every clinical trial that's going on in the United States. So, that's an enormous amount of information to sift through. But, you can never have too much information, and you're often better off starting with a large amount of information and narrowing it down.

When applying for clinical trials, you will probably be submitting more than one application. Be sure to keep a spreadsheet or some kind of list to keep track of the trials you've already researched, the ones you've applied for, and the responses that you get. Understanding the responses, especially, helps you to improve the quality of future applications. And, it can help you to avoid wasting precious time effort applying for trials that you're not even qualified for.

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Stem Cell Therapies for Spinal Cord Injuries

Spinal Cord Stem Cells Comments Off on Stem Cell Therapies for Spinal Cord Injuries | October 17th, 2020

Immuno-oncology and CAR T cells energized the field of regenerative medicine, but for cell and gene to deliver on their promises, new, disruptive technologies and new modes of operation are needed. Specifically, that entails improving manufacturing to control variables and thus ensure product consistency, and maturing the regulatory environment to improve predictability.

Manufacturing cells is not like manufacturing small molecules, Brian Culley, CEO of Lineage Cell Therapeutics, told BioSpace. For cell therapy products to mature into real products that deliver on the promises of 10 years ago, they must be scalable which drives affordability and they must solve their purity issues.

On the clinical side, cell and gene therapies must find places where small molecules, antibodies or other traditional approaches may not be the best option.

For example, The era of transplant medicine is unfolding before us, Culley said. Because of the transplant component, cell therapy may enable changes the body never could do alone.

Lineage is addressing dry AMD and spinal cord injuries with two of its therapeutics.

Our approach is fundamentally different from traditional approaches. We replace the entire cell rather than modulate a pathway. There is a rational hypothesis where cell therapy can win, but first we need to fix the operational hurdles, Culley said.

To address the manufacturing challenges, Culley said, We work only with allogeneic approaches. For us, not being patient-specific is a huge advantage.

Not long ago, the industry was focused on 3D manufacturing in bioreactors.

Were beyond that, Culley said. For our dry AMD product, we can manufacture 5 billion retinal cells in a three liter bioreactor. The advantage is that the cells exist in a very homogenous space and are 99% pure.

As a result, they are more affordable and can be harvested with little manipulation.

Manual manipulation affects gene expression, he pointed out, so minimizing that, as well as the vast quantities of plastics typically required, results in a more controlled process and a more consistent product.

Additionally, Lineage introduced a thaw and inject formulation, so the cell therapy can be thawed in a water bath, loaded into a chamber and injected, all within a few minutes. Traditional dose administration requires washing, plating and reconstituting the cells the before they are administered to a patient.

Getting rid of the prior day dose prep is one example of the maturation of the field, which we are deploying today to help usher in a new branch of medicine, Culley said.

At Lineage, were tackling problems that largely were intractable. For dry AMD, theres nothing approved by the FDA. No one know why the retinal cells die off, so we manufacture brand new retinal cells (OpRegen) and implant them, Culley said. Were seeing very encouraging clinical signs, including the first-ever case of retinal restoration.

Retinal cells compose a thin layer in the back of the eye, Culley explained.

They start to die off in one spot, and that area grows outward. When we inject our manufactured cells where the old ones died, weve seen the damaged area shrink and the architecture in previously damage areas completely restored, Culley said. Weve treated 20 patients for dry AMD in, ostensibly, safety trials, but you cant help but notice efficacy when a patient reads five more lines on an eye chart. Its hard to imagine our intervention wasnt responsible for that, especially when humans cant regenerate retinal tissue.

The spinal injury program (OPC1) may represent an even greater breakthrough. As with dry AMD, there is no FDA-approved therapy.

We manufacture oligodendrocytes and transport them into the spinal cord, to help produce the myelin coating for axons, he told BioSpace. Because of the oligodendrocytes, the axons grow, become myelinated, and begin to function. Small molecule and antibody therapies havent been able to do that.

So far, 25 people have been treated in a Phase I/II trial. Culley reported cases in which a quadriplegic man, after OPC1 therapy, is now typing 30 to 40 words per minute, and another who now can throw a baseball. Its not unusual for patients who initially were completely paralyzed to now schedule their treatments around college classes, Culley said.

Humans can have varying degrees of recovery from spinal cord injury, but these are higher than we would expect, Culley said.

Other cell and gene companies are advancing solutions, too.

Many companies with induced pluripotent stem cells (iPSCs) are trying to figure out how to get scalability, purity, and reproducibility to work for them. Its not a quick fix, he said.

One of the challenges is balancing the clinical and manufacturing aspects of development.

If you have a technology thats not yet commercially viable, but you have clinical evidence, its tempting to focus on the clinical side, Culley said.

Too many companies do that, and then find their candidate must be reworked for scale up. Therefore, consider scale up and manufacturing early.

Theres a need for balance at a more granular level, too. For example, he asked, How many release criteria do you need? Just because you know a cell expresses a certain surface marker, does that add to your process? Ive seen companies ruined by trying to be perfect, and others by rushing headlong, seeing evidence where evidence doesnt exist.

As Lineage matures its processes to support larger clinical trials, the greatest challenges have been time It takes 30 to 40 days to grow cells, Culley said and regulatory uncertainty. Often, there is no regulatory precedence so there are holes to be addressed. For example, cell and gene therapies sometimes have a delivery component such as a scaffold or delivery encapsulation technology that also must be considered. Real-time regulatory feedback isnt available, so you proceed, presuming that what youre doing will be acceptable to regulators.

The FDA recognizes that new, disruptive technologies and approaches are being used, and must be used, for cell and gene therapy to reach patients.

The FDA is responsive and is trying to push guidance out, Culley said, but it takes time.

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Disruptive Technologies and Mature Regulatory Environment Vital for Cell Therapy Maturation - BioSpace

Spinal Cord Stem Cells Comments Off on Disruptive Technologies and Mature Regulatory Environment Vital for Cell Therapy Maturation – BioSpace | October 17th, 2020

Sixteen years ago, voters were promised that $3 billion of bonds for embryonic stem-cell research would deliver cures for diseases such as diabetes, Alzheimers, Parkinsons and heart disease.

Instead, weve gotten cures or potential treatments for a very different and unexpected set of afflictions, such as a deadly immune disorder, spinal cord injury, a type of cancer and a form of blindness.

The moral of the story as Californians decide whether to continue support by approving Proposition 14s nearly doubled research budget of $5.5 billion is this: Science marches to its own beat and on its own clock, awe-inspiring but oblivious to political pledges.

We got things, but not necessarily what we expected, said Hank Greely, director of Stanfords Center for Law and the Biosciences. Its saving lives, but not in the way most people thought.

Without Proposition 71, the ambitious 2004 ballot measure that first paid for the stem-cell research, 8-year-old Evangelina Vacarro of Corona might be in a casket, rather than skateboarding, horseback riding and playing in the dirt with her pet terrier Daisy.

The engaging hazel-eyed child was born with a rare disease that left her unable to fight off infections. In a clinical trial funded by the state initiative, scientists corrected the deadly genetic flaw that disabled her immune system and restored her to health.

Jake Javier, a biomedical engineering student at Cal Poly, might be unable to live independently. Paralyzed in a diving accident, the 22-year-old gained some function in his arms and hands after the introduction of specialized neural cells in a clinical trial funded by Proposition 71.

It completely changed the trajectory of my life, said Javier, of San Ramon.

Sandra Dillon, a San Diego graphic designer diagnosed at age 28 with a rare form of blood cancer called myelofibrosis, is now in remission after treatment with an FDA-approved drug that was identified through Prop. 71 funding. No longer hospitalized, shes backpacking and surfing.

Before injection with stem cells to combat progressive blindness caused by retinitis pigmentosa, Rosie Barrero of Los Angeles could only see shadows. Now she can discern the time on her cell phone, the colors of kitchen cups and the faces of her family.

In addition to these and more than 60 other clinical trials, the California Institute for Regenerative Medicine (CIRM) created under Proposition 71 has led to about 3,000 peer-reviewed research papers and 974 patents or patent applications.

It has helped bankroll 12 elegant research facilities, donating $43 million to Stanford for the Lorry I. Lokey Stem Cell Research Building, $20 million to the Buck Institutes Regenerative Medicine Research Center in Novato, $20 million to UC Berkeleys Li Ka Shing Center and $35 million to UCSFs Regeneration Medicine Building. It funded five stem cell-focused clinics at hospitals to accelerate the delivery of therapies.

It has generated $293.6 million in direct income and taxes on corporate profits and sales of equipment and supplies, according to an estimate by research professors Dan Wei and Adam Rose of the University of Southern California.

And it has vaulted California to a leadership role in the nations stem-cell science.

CIRM has supported some really superb research and researchers and built a powerful infrastructure, said Robert Cook-Deegan of the School for the Future of Innovation in Society at Arizona State University. In a field where there arent as many other sources of funding, thats almost certainly, in the long run, a good thing.

This is stunning progress for an effort that faced bleak prospects after then-President George W. Bushs federal funding restrictions on embryo research.

Still, it falls far short of Proposition 71s breathless rhetoric from the 2004 campaign.

Stem Cell Research: Breakthrough cures for diseases that affect millions of people, asserted the campaign literature. In a 30-second commercial, actor Michael J. Fox, diagnosed with Parkinsons disease, urged voters to please support the effort to find cures, to save the life of someone you love. Other A-list celebrities, as well as more than 20 Nobel Prize-winning scientists, also promoted it.

Prop 71 will help reduce skyrocketing health care costs, the campaign promised.

The measure was tied up by litigation and the effort got off to a late start. Now, one-third of the way through the bonds 35-year payback period, its nowhere near yielding the $2.2 to $4.4 billion in projected state revenues or $1.1 billion in royalty revenues. To date, only $517,989 in royalties has been paid to the state general fund.

And with only two products FDA-approved and no therapies yet in widespread use, theres so far no evidence that Proposition 71 has delivered the anticipated $3.4 to $6.9 billion state health care savings and $9.2 to $18.4 billion in savings for other payers.

Initial CIRM funding created fewer California jobs than expected: 27,208 jobs per year, according to the USC report, rather than the estimated 47,000 jobs per year.

There have been clinical challenges. A cure for diabeteshas been tougher than expected: A promising approach has lagged because the bodys immune system rejects the pouch that holds implanted, insulin-producing cells. A leukemia cure, seemingly around the corner, has been stymied because blood-forming stem cells are stubbornly reluctant to multiply.

If it all worked, it wouldnt be research, said Stanfords Greely. Politics has a corrupting influence on everything it pushes toward exaggeration.

There have also been business failures. More than $5 million was invested in a promising brain cancer treatment called ICT-107, but efforts were abandoned when company ImmunoCellular Therapeutics ran out of money. Another $3 million was for naught when company Neostem couldnt find funding and swapped CEOs, dropping its melanoma treatment CLBS20.

Even some home runs, such as Gileads recent $4.9 billion deal for the CIRM-supported immuno-oncology biotech Forty Seven, offer taxpayers relatively little payoff. While CIRM expects royalties from Gileads future cancer cure, it didnt benefit from an explosive jump in share prices because the state Constitution bars state agencies from holding stock in private companies.

I think the big downside of CIRM has been the overpromising of how fast things would happen and the form that the return would take, said Cook-Deegan. The commercial potential may be real in the long runbut it was oversold with shorter time horizons than are actually practical.

Proposition 14 will cost far more: $7.8 billion $5.5 billion in principal and $2.3 billion in interest by the time the bonds are repaid. The total cost of Proposition 71 is $3.54 billion, or more than $4 billion when adjusted for inflation. The increase is necessary due to the soaring cost of clinical trials, said Robert Klein, the author of both measures

As voters consider whether to support the new proposition, its unfair to measure it against the prior propositions current trajectory, because medicine reaps its greatest rewards many years after the initial investment, said Klein. It takes 12 to 15 years, on average, to go from discovery to therapy.

It would be similar to judging the Apollo 11 mission when the capsule was a little past a third of the way to the moon and find it coming up short because not one of the three astronauts had set foot on the lunar surface, said Klein.

But critics say Proposition 14 commits California to spending money it does not have. It adds future debt, while education, health care and housing are underfunded.

While I think CIRM has done good work, and I support stem-cell research, the state is facing a huge budget deficit, said Jeff Sheehy, a CIRM board member. And the new measure fails to ensure that the state gets a return on its investment. Instead, it is a giveaway to pharma and biotech.

Theres no longer a compelling rationale for California to support the research because the federal ban has been lifted, with NIH spending about $300 million a year on embryonic stem-cell research, he said.

If the new proposition is rejected by voters, CIRM will begin closing its doors this winter and ongoing research may crash, said Dr. Larry Goldstein, director of the UC San Diego Stem Cell Program.

If these trials get killed because of lack of funding, there is no guarantee that we will get them back up and running again, even if they look really promising, Goldstein said. It will be hard to find financing for them.

Proposition 71 launched the beginning of embryonic stem-cell research and Proposition 14, despite the steep price tag, should continue that momentum, say proponents.

There is no dollar amount you can put on having a healthy child, said Alysia Vaccaro, Evangelinas mother. There is no price for that.

Prop 71, by the numbers:

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Should California invest $5.5 billion more into promising ...

Spinal Cord Stem Cells Comments Off on Should California invest $5.5 billion more into promising … | October 17th, 2020

President Trump has benefitted from decades of medical research using human fetal tissue, and so have you.

When he got sick with the coronavirus in September, Trump's Regeneron antibody treatment had been developed with the use of HEK 293T cells, which have been a workhorse material on biomedical lab benches around the world, since they were first cultured from an embryonic kidney cell in the Netherlands in the early 1970s.

Even so, Trump and his administration have cracked down on new fetal tissue research being done today in the US dampening hopes the same kinds of cells that helped create his treatment may continue being used in new research, to pave the way toward future treatments and cures for millions of people.

The ban could have a crippling effect on the hunt for treatments for neurodegenerative diseases, and new drug therapies for cancers and HIV. It's also affecting the way scientists study viruses that cause disease in humans, a critical impairment during the coronavirus pandemic.

The truth is, there is no great alternative (yet) for human fetal tissue in medical research. (Humans, and their development, are kind of complicated.) So, for now, we're missing out on an unknown number of medical advances, as the raw materials for this research get discarded after miscarriages and abortions.

"Scientists, such as myself, think that it's better for all of that tissue to go to research, than to just destroy it," Professor Lawrence Goldstein, a neuroscientist at UC San Diego, who has used fetal tissue to study Alzheimer's in the past, said.

Here's why.

Dr. Scott Kitchen, associate professor of medicine and Director, UCLA CFAR/JCCC Humanized Mouse Core Laboratory, in the vivarium mice room at the UCLA campus in Los Angeles, California on November 15, 2019. Philip Cheung for The Washington Post via Getty Images

"Most drugs and most vaccines have, at some point in their movement towards the clinic, passed through a stage in which they've been either developed or tested using cell lines that came from human fetal tissue," said Dr. Mike McCune, an HIV researcher who, in the 1980s, developed the first mice engineered to study human diseases using fetal tissue.

In McCune's lab, fetal tissue has been used to test out drug treatments that have turned HIV from a death sentence into a livable, chronic disease. Today, many branches of medical research, treating everything from cancer, to spinal cord injuries, Alzheimer's, and organ transplants have all, in some way, benefitted from fetal tissue research.

One of the most basic ways that fetal tissue has been used is in the creation of prolific cell lines (like the ones Regeneron's used in its labs) which can be dispatched indefinitely to test out how well treatments or vaccines might work, before they go inside people.

Such cell lines are also sometimes used not just to test, but to create treatments. Take the advent of the polio vaccine, which has prevented millions of cases of paralysis, and saved hundreds of thousands of lives. That was once grown inside fetal cells, as were many other vaccines.

Fetal tissue is also used as a gold standard comparison tool. For example, in organ development, it's used to make sure that stem cells being developed into artificial organs are mimicking real, human, cells in the proper way.

Studying human fetal tissue also helps researchers better understand the reasons why birth defects arise, and glean insights into how these congenital issues may be better prevented in the future.

During the coronavirus pandemic, fetal tissue could be used to develop precise human immune system models which could then be used to quickly try out drugs, determining within weeks which might work, and which are duds.

Today, there is no reliably good alternative material to use for fetal tissue, the very makings of our humanness. Fetal cells are less specialized than fully-formed human cells, and as such, they are much more flexible tools than our own cells for using in the lab, and studying all kinds of diseases that only affect us.

Donating fetal tissue is a lot like organ donation. There are strict rules in place to ensure no exchange of money or favor occurs. Instead of being incinerated, then, that fetal tissue may be used in a lab.

"You have a family, a mother, or parents, who make the decision that they want something good to come out of this tragedy of losing, or terminating, a pregnancy," virologist Alexander Ploss, who does work on fetal stem cells at Princeton University, told Insider of fetal tissue donation. "We're basically now potentially restricting this option, and taking this option away."

Dr. Lindsey Baden, right, bumps elbows with COVID-19 vaccine trial participant Anthony Shivers at Brigham and Women's Hospital in Chestnut Hill, Massachusetts on October 8, 2020. Craig Walker/The Boston Globe via Getty Images

Fetal tissue was already given the Congressional thumbs up by a bipartisan group of lawmakers in 1993.

The vote in the Senate that year was near-unanimous: 93 to 4, with anti-abortion senators Mitch McConnell and Chuck Grassley both voting "yes". They acknowledged there are clear benefits to humanity in using this tissue, just as the National Institutes of Health did, as recently as 2018.

The National Catholic Bioethics Center has for years, likewise, agreed that there are benefits to using fetal cell lines and tissues.

The NCBC said as recently as May 2020 on its website that "one is morally free to use the vaccine, despite its historical association with abortion, if there is a proportionately serious reason for doing so."

"This is especially important for parents," the NCBC added, "who have a moral obligation to protect the life and health of their children, and those around them."

But on June 5, 2019, the Department of Health and Human Services stopped funding all new human fetal tissue research, effectively shutting down the last private labs (in California and Montana) that were using federal dollars for fetal tissue work.

"Many of the researchers who may be most affected by this policy change study pathways and processes associated with disease in infants and children," professor Carolyn Coyne, who studies viruses that affect fetal and neonatal health, wrote in the Washington Post at the time. "As such, the only certain consequence of the new policy is that it will impede medical discoveries that could advance new treatments to save the lives of infants, the very lives those in favor of this policy claim they are trying to protect."

Juan Duran-Gutierrez kisses his newborn baby girl Andrea for the first time in his home after bringing her home from the hospital, August 5, 2020. Duran-Gutierrez's wife and Andrea's mother, Aurora, died from COVID-19 in July. Elizabeth Flores/Star Tribune via Getty Images

The NIH can technically still fund work on fetal tissue outside its own walls, but the agency has been hamstrung by a new fetal tissue advisory board, largely comprised of members with strong antiabortion group ties. At a recent meeting, the group approved just one of 14 fetal tissue grant proposals up for review, The Washington Post reported. It was a grant to study whether an alternative to fetal tissue works as well.

"The administration has developed a policy that the evangelical and hardcore pro-life community wants, which is a complete ban on the use of any federal funds for new fetal tissue," Goldstein, who sat on the recent NIH committee, told Insider. "You know, they're okay with the old stuff."

Antiabortion groups have largely shrugged off the fact that Trump's coronavirus treatment benefitted from medical research on fetal tissue, decades ago.

Goldstein sees this as pure hypocrisy.

"The claim they're making is that, 'well, it was done a long time ago, so it's okay now,'" he said. "Well, you know, that's not really morally very consistent. You're going to block us from developing new therapies with fetal tissue, but you're going to be okay using the ones that are already here?"

Goldstein says there are three main reasons to continue using fetal stem cells: One, there's no evidence that this research incentivizes anyone to have an abortion. Two: "it's really valuable research" which has saved and improved countless lives. And three: "The alternative is throwing it in the trash," he said. "How is that a dignified use of the material?"

"I don't know if that's going to persuade anybody, but those are the factors I'd cite," he added.

Dr. Mustafa Gerek is vaccinated in volunteer in trials of a COVID-19 vaccine from China at Ankara City Hospital in Ankara, Turkey on October 13, 2020. Aytac Unal/Anadolu Agency via Getty Images

The coronavirus isn't the only area where scientists now have a blind spot.

"There's a whole bunch of genetic diseases that we don't understand very well, neuro-developmental disorders that we don't understand very well, for which actually having access to, let's say, human neuronal tissue, or whatever it may be, is absolutely critical," Ploss said.

"I'm not particularly optimistic that it's possible right now to obtain any serious funding, federal funding, for this kind of research," he said. "It's pretty much impossible right now to get any kind of funding for research that involves human fetal tissue."

But, he says, the stakes are so high that he'll still try, in the coming months. He, and all the other scientists Insider spoke to for this story are already worried about the US losing some of its competitive edge in biotech.

"The reason we are a world leader is because we have been innovative, we have rewarded innovation, and for the most part, the government has stayed out of the way, except funding high-quality research, that's been competitively reviewed," Goldstein said.

"We are always at risk of losing our advantage to an aggressive competitor, and I don't want to see that happen. I'm a loyal American, and I want to see us be the best."

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What is human fetal tissue research and why is it done - Business Insider - Business Insider

Spinal Cord Stem Cells Comments Off on What is human fetal tissue research and why is it done – Business Insider – Business Insider | October 17th, 2020

Skin is a complex, living organ made up of several structural components that (quite literally) touches a lot of different parts of us. When you look at the makeup, there's collagen, elastin, hyaluronic acid, ceramides, lipids, and so forth; from there, it's also affected by the muscle composition and bone underneath. This is all to say, when wrinkles formit's hardly ever due to a singular reason.

So to start, there is the fact that many components of our skin structure decline with age. "As we age, we lose collagen, fat, and start to resorb bone. These changeslead to volume loss, thin, saggy skin. As a result, our nasolabial folds become more pronounced," says Lolis.

It's also important to note that these lines are exacerbated with movement, the same way crow's feet can come from squinting and the "11's" can come from scrunching yourbrow. "Laugh lines are formed by constant use of the orbicularis orbis muscle which allows us the ability to speak," says Masur. "Over time as we age the skin protecting this muscle becomes stretched creating laxity increasing the appearance of these folds. The region around the mouth known as the peri-oral area is one of the thinnest-skinned on the face, making us more susceptible to fine lines or wrinkles forming the 'laugh lines.'"

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Laugh Lines Are Totally Normal How To Ease Them Sans Injections - mindbodygreen.com

Skin Stem Cells Comments Off on Laugh Lines Are Totally Normal How To Ease Them Sans Injections – mindbodygreen.com | October 17th, 2020

Market Report Summary

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The healthcare industry has been focusing on excessive research and development in the last couple of decades to ensure that the need to address issues related to the availability of drugs and treatments for certain chronic diseases is effectively met. Healthcare researchers and scientists at the Li Ka Shing Faculty of Medicine of the Hong Kong University have successfully demonstrated the utilization of human induced pluripotent stem cells or hiPSCs from the skin cells of the patient for testing therapeutic drugs.

The success of this research suggests that scientists have crossed one more hurdle towards using stem cells in precision medicine for the treatment of patients suffering from sporadic hereditary diseases. iPSCs are the new generation approach towards the prevention and treatment of diseases that takes into account patients on an individual basis considering their genetic makeup, lifestyle, and environment. Along with the capacity to transform into different body cell types and same genetic composition of the donors, hiPSCs have surfaced as a promising cell source to screen and test drugs.

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In the present research, hiPSC was synthesized from patients suffering from a rare form of hereditary cardiomyopathy owing to the mutations in Lamin A/C related cardiomyopathy in their distinct families. The affected individuals suffer from sudden death, stroke, and heart failure at a very young age. As on date, there is no exact treatment available for this condition.

This team in Hong Kong tested a drug named PTC124 to suppress specific genetic mutations in other genetic diseases into the iPSC transformed heart muscle cells. While this technology is being considered as a breakthrough in clinical stem cell research, the team at Hong Kong University is collaborating with drug companies regarding its clinical application.

The unique properties of iPS cells provides extensive potential to several biopharmaceutical applications. iPSCs are also used in toxicology testing, high throughput, disease modeling, and target identification. This type of stem cell has the potential to transform drug discovery by offering physiologically relevant cells for tool discovery, compound identification, and target validation.

A new report by Persistence Market Research (PMR) states that the globalinduced pluripotent stem or iPS cell marketis expected to witness a strong CAGR of 7.0% from 2018 to 2026. In 2017, the market was worth US$ 1,254.0 Mn and is expected to reach US$ 2,299.5 Mn by the end of the forecast period in 2026.

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Customization to be the Key Focus of Market Players

Due to the evolving needs of the research community, the demand for specialized cell lines have increased to a certain point where most vendors offering these products cannot depend solely on sales from catalog products. The quality of the products and lead time can determine the choices while requesting custom solutions at the same time. Companies usually focus on establishing a strong distribution network for enabling products to reach customers from the manufacturing units in a short time period.

Entry of Multiple Small Players to be Witnessed in the Coming Years

Several leading players have their presence in the global market; however, many specialized products and services are provided by small and regional vendors. By targeting their marketing strategies towards research institutes and small biotechnology companies, these new players have swiftly established their presence in the market.

Explore Extensive Coverage of PMR`sLife Sciences & Transformational HealthLandscape

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics and market research methodology to help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

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Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 - The Think Curiouser

Skin Stem Cells Comments Off on Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 – The Think Curiouser | October 17th, 2020

Switch up your regular makeup routine for a more naturally radiant look by switching to CC cream. Its perfect for days when you want lighter coverage, or you can use it as a primer. The benefit of CC cream is that it works both harder and smarter for you. Often, they contain extra nourishing ingredients to boost your hydration and sun protection to prevent damage from harmful UV rays. Plus, they use color-correcting technology and pigments to even out skin tone, cover blemishes, and diminish the look of fine lines and wrinkles. Its a great alternative or addition to your foundation for an easy, glowy, radiant look.

Put your best face forward with the Super CC Cream from Physicians Formula. It contains micro color-correcting pigments and anti-aging ingredients to even out skin tone and to reduce the appearance of fine lines, age spots, and dullness. Plus, youll get a good dose of moisturizing elements, as well as SPF 30 that protects your skin from additional sun damage. The formula is lightweight and blends easily, making application quick and straightforward, leaving your skin feeling smooth and youthful.

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Chanels CC Cream packs a punch in correcting signs of aging and proving beautifully light coverage. It is infused with extracts from the murunga plum, a native Australian superfruit. This plant is rich in vitamin C and antioxidants for improving texture and glow while protecting the skin from free radicals. The broad-spectrum sunscreen component covers you for both UVA and UVB damage. Meanwhile, the addition of hyaluronic acid draws moisture to the skin for a plump, youthful look. With continual use, your skin will look younger, healthier, and more radiant.

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Enjoy 24-hour hydration with this CC cream formula from Lancome. It contains SPF50 physical sunscreen, as well as mineral filters for full-coverage color correction. Improve your skin texture, minimize pores, balance uneven skin tone, and reduce the appearance of fine lines and wrinkles, all in one easy step. It also has an antioxidant complex, vitamin E, and mint-extract to add additional environmental protection, hydration, and an energizing feel.

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Giorgio Armani brings cutting-edge technology and the expertise of makeup artist Linda Cantello together in this Prima Color Control Glow Moisturizer. Enjoy long-lasting hydration from vitamin E, moringa oleifera extract, and adenosine. When it comes to coverage, the five shades adapt to the skins color to enhance the natural luminosity while hiding blemishes and fine lines. Plus, added menthol-based ingredients leave you feeling refreshed and awake, ready to tackle the day ahead.

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If youre looking for a CC cream that does more for you, the Bare Minerals Complexion Rescue is an excellent option. Youll not only get radiant coverage but sun protection and long-lasting skincare benefits. The oil-free, water-infused formula keeps the skin hydrated for up to 12 hours after application, and with continual use, can boost the skins overall hydration. Made with 97% naturally derived ingredients, the gel-cream texture feels light and smooth on the skin. Lastly, there are 20 flexible shades to choose from, which naturally adapts to your skin tone.

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Get glowing skin by using Cliniques Moisture Surge CC Cream. The oil-free formula provides a shot of hydration, so your skin looks good from the inside out. Next, it instantly color corrects to diminish any redness, dullness, or imperfections, giving you a healthy vibrance. A sun protection factor of 35 prevents additional damage from harmful UV rays, yet the formula is lightweight and feels beautiful on the skin. Use it on its own for an easy, glowy vibe, or add additional foundation for a full-coverage look.

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Youll be feeling and looking fresh as a daisy with Supergoops Daily Correcting CC Cream. It contains brightening ingredients such as apple extract and mica, which reflects the light to give you a youthful, glowy look. Vitamin C and alpha-hydroxy acids keep the skin smooth, while sodium hyaluronate is a humectant that draws moisture into the skin, keeping you hydrated. Wear this CC cream daily to minimize skin discoloration, dryness, fine lines, and blotchiness. Plus, the SPF 35 UV protection is mineral-based, rather than chemical, making it suitable for sensitive skin types.

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Nourish, hydrate, and protect your skin all in one step by using Olays lightweight Total Effects Tone Correcting CC Cream. It feels light on your skin while still providing a heavy dose of beneficial ingredients. There are seven vitamins and antioxidants for extra protection, including vitamin B3 and VitaNiacin Complex II, both of which improve the skins appearance and repairs the barrier. It also corrects your skin tone, diminishes fine lines, and minimizes the pores. You can use this product in place of both your moisturizer and foundation, as well as sunscreen, thanks to the SPF 15.

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Choose from eleven different shades in IT Cosmetics inclusive CC+ Cream range. This foundation replacement corrects any color imbalances and pigmentation issues, as well as hydrates and protects your face from the sun and environmental aggressors. It was developed in collaboration with plastic surgeons to ensure you get the most benefit. Its chock full of active ingredients, including niacin, peptides, hydrolyzed collagen, and hyaluronic acid, as well as antioxidants and minerals. Combined, these ingredients hydrate, reduce the appearance of acne scarring and wrinkles, evening out skin tone, tackling dark under-eye circles, and minimizing large pores. The result is a flawless, radiant complexion that wont crack or crease, leaving you feeling beautiful and confident.

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Fruit stem cells and vitamin C come together in this lightweight CC cream. Youll enjoy beautiful tinted coverage that easily replaces your foundation when you feel like a more natural look. It also reduces the appearance of fine lines and wrinkles while evening out skin tone and texture. Plus, you need not worry about sun damage, with broad-spectrum SPF 30 protection from UVA and UVB rays. There are seven shades to choose from, ranging from Natural Glow to Deep Glow.

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Enjoy medium coverage with the Ultra CC Cream from Pacific Store. This illuminating formula contains coconut water, kelp, and ginseng for a light, smooth finish that rehydrates your skin. The color correcting minerals even out your skin tone and hide any blemishes, while the SPF 17 physical sunscreen protects your skin from UV damage. Plus, its vegan, cruelty-free, and comes in a 100% recyclable container.

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Cle Cosmetics adds an extra element to their CCC cream a color control and change cream. This product can replace both your primer and foundation, as well as sunscreen, thanks to the powerful SPF50. It offers more substantial coverage than regular CC creams and matches flawlessly to your skin using unique Micro Capsule Technology. Plus, it comes in ten different, inclusive colors, so no matter your skin tone, you can rock a dewy, moisturized complexion all day long.

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Protect and hydrate your skin while looking fabulous. The Honest Beauty Clean Corrective cream is a six-in-one formula that primes, perfects, protects, blurs, brightens, and moisturizes. It boasts vitamin C to improve skin tone, as well as an antioxidant blend to protect from environmental damage. Physical sunscreens also shield your skin from sun damage, with a sun protection factor of 30. Plus, it provides blue light defense and is vegan and cruelty-free.

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Embrace smoother, beautiful skin with Alamys Smart Shade CC cream. It features color correction technology that reduces imperfections, discoloration, and dullness while providing a boost of hydration. It also adjusts to your natural skin tone. Meanwhile, the SPF35 protects your face from the suns damaging rays. Lastly, the hypoallergenic, fragrance-free formula also makes it great for anyone with more sensitive skin.

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This mattifying tinted moisturizer from black Up is designed specifically for black women and people of color with darker skin tones a segment of the beauty market often left out of CC cream shades. You can use it on its own as a lightweight foundation or put it to work as a primer. In one simple step, it evens out skin tone, targets dark spots and excess sebum, and improves the natural radiance of the skin. Plus, it adds a boost of hydration to keep your skin feeling smooth and supple.

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The best CC cream will combine high levels of hydration and protection, as well as match your skin tone. You want both sun protection in the form of sunscreen and protection from environmental aggressors by including vitamins and antioxidants. Look for brands like Physicians Formula, Supergoop!, and IT Cosmetics. If you have darker skin, look for inclusive brands such as IT Cosmetics, black Up, and Cle Cosmetics.

The BB stands for beauty balm or blemish balm. It's very similar to CC cream in that it combines the benefits of skincare with makeup to give you light coverage for a simple, natural look, or as a primer. You'll enjoy hydrated, illuminated skin with regular use. This most significant difference is that it doesn't provide comprehensive coverage, so if you need more, then a CC cream or foundation will be the better option.

CC cream stands for color corrector or complexion corrector cream. It's a lightweight alternative to foundation or can be used in conjunction with it, as a primer. It often contains nourishing ingredients to boost hydration, sun protection elements, and color-correcting technology. It's the best of both worlds, combing skincare and makeup into one fantastic product.

You can use a primer in addition to CC cream, but it's not always necessary. Primer acts to fill in and smooth out imperfections but doesn't necessarily provide additional benefits such as moisturizing or sun protection. Meanwhile, CC cream corrects discoloration and smooths out the skin, while giving that extra protection. If you have heavy acne scarring or deeper wrinkles, a primer will still be beneficial. However, if you're looking to even out your complexion and increase hydration, the CC cream will be sufficient by itself.

CC cream stands for color corrector or complexion corrector cream. It's lighter weight than foundation but provides more coverage than BB cream. All you need to do is substitute it for your foundation in your makeup routine, or use it as a primer. Start with a cleansed, toned, and moisturized face. Then using a beauty blender or your fingertips, apply the liquid all over your face, ensuring you're fully smoothed out around the edges, building up the coverage as you desire.

You can use CC cream on the days where you're not vibing a full face of makeup but still want some coverage. It's great when you're running behind schedule or just a bit time-poor. You can also use it as a primer under your regular foundation. CC Cream eliminates steps in your makeup routine, such as using a separate sunscreen, color corrector, and foundation, which can save you time in the morning.

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15 Best CC Creams for a Flawless Complexion - The Trend Spotter

Skin Stem Cells Comments Off on 15 Best CC Creams for a Flawless Complexion – The Trend Spotter | October 17th, 2020

In summary

Proposition 14 asks voters to spend nearly $8 billion to continue the stem cell research program at a time when the coronavirus pandemic has decimated the state budget.

For the second time in 16 years, California voters will decide the fate of the states multi-billion dollar stem cell research program that established the state as a worldwide leader.

How the times have changed.

In November, as the pandemic drags on, Proposition 14 asks voters to spend nearly $8 billion to continue the program during a period when the research environment has significantly evolved and coronavirus has battered the states budget.

The bond measure would approve $5.5 billion in bonds to keep the states stem cell research agency running and grants flowing to California universities and companies.

At least $1.5 billion would be earmarked for brain and central nervous system diseases like Alzheimers and Parkinsons. The overall cost of the bonds and their interest totals about $7.8 billion, according to the state legislative analyst. The state would pay about $260 million annually for 30 years, or about 1 percent of Californias annual budget.

Proposition 14 is essentially a repeat with a bigger price tag and a few tweaks of Proposition 71, which California voters approved in 2004 after then-President George W. Bush prohibited, on religious grounds, all federal funding of any stem cell research using human embryos.

The bond measure would approve $5.5 billion in bonds to keep the states stem cell research agency running and grants flowing to California universities and companies.

That groundbreaking measure authorized $3 billion in state bonds to create the states stem cell research agency, the California Institute for Regenerative Medicine, and fund grants for research into treatments for Alzheimers disease, cancer, spinal cord injuries and other diseases.

The institute has nearly used up its original funding, so Prop. 71s author, real estate investor and attorney Robert N. Klein II, led a new effort to get Prop. 14 on the November ballot.

This time, embryonic stem cell research is in a much different place, with federal funding no longer blocked and more funding from the biotech industry.

Voters will want to consider what Californias previous investment in stem cell research has accomplished. Its a nuanced track record.

While many scientific experts agree that Prop 71 was a bold social innovation that successfully bolstered emerging stem cell research, some critics argue that the institutes grantmaking was plagued by conflicts of interest and did not live up to the promises of miracle cures that Prop. 71s supporters made years ago. Although the agency is funded with state money, its overseen by its own board and not by the California governor or lawmakers.

The agency had done a very good job of setting priorities for stem cell research, including research using human embryos, and doling out $300 million annually to build up California as a regenerative medicine powerhouse, according to a 2013 evaluation by the National Academies of Science, Engineering and Medicine.

But the report also found that because the institutes board is made up of scientists from universities and biotech firms likely to apply for grants, board members had almost unavoidable conflicts of interest.

Because human stem cells can develop into many types of cells, including blood, brain, nerve and muscle cells, scientists have long looked to them for potential treatments for currently incurable diseases and injuries. Researchers use two types of stem cells: embryonic stem cells, derived from unused human embryos created through in vitro fertilization, and adult stem cells, which are harder to work with but in some cases can be coaxed in a lab into behaving more like embryonic stem cells.

From the start, stem cell research has been ethically charged and politically controversial because human embryos are destroyed in some types of studies. Federal restrictions on the research have waxed and waned, depending on which political party holds power. While former President Bush restricted federal money for embryonic stem cell research, former President Obama removed those restrictions.

The Trump administration has restricted government research involving fetal tissue but not embryonic stem cells. However, anti-abortion lawmakers have called on the President to once again end federal funding for embryonic stem cell research.

California-funded research has led to one stem cell treatment for a form of Severe Combined Immunodeficiency known as the bubble baby disease. Children with the rare disease dont make enough of a key enzyme needed for a normal immune system. Without treatment, they can die from the disease if not kept in a protective environment. The U.S. Food and Drug Administration is now reviewing the treatment but has not yet approved it for widespread use.

Although many of the agencys early grants were for basic science, the institute also has supported 64 clinical trials of treatments for many types of cancer, sickle cell disease, spinal cord injuries, diabetes, kidney disease and amyotrophic lateral sclerosis, commonlyknown as Lou Gehrigs disease.

A June 2020 analysis by University of Southern California health policy researchers estimated that taxpayers initial $3 billion investment in the research institute helped create more than 50,000 jobs and generated $10 billion for the states economy.

Gov. Gavin Newsom has endorsed Proposition 14, and other supporters include the Regents of the University of California, the California Democratic Party, the Juvenile Diabetes Research Foundation, patient advocacy groups like the March of Dimes, and some local politicians and chambers of commerce.

Supporters have raised more than $8.5 million, including about $2 million from billionaire Dagmar Dolby, to pass the measure, according to California Secretary of State campaign finance reports.

The passage of Proposition 71 helped save my life, Sandra Dillon, a blood cancer patient, wrote in a San Diego Union-Tribune commentary supporting Proposition 14. She wrote that she had benefited from a drug developed with Institute-funded research that has been designated by the FDA as a breakthrough therapy.

It is unimaginable to think that Californians would vote to discontinue this amazing effort I dont know where I would be or what condition I would be in if it wasnt for the investment Californians made nearly two decades ago.

I think the agencys done good work, but this was never planned to be funded forever with debt.

Lawrence Goldstein, a UC San Diego professor of cellular and molecular medicine and stem cell researcher, said the grants were instrumental in furthering his research on treatments for Alzheimers disease and that Prop. 14 will help create new jobs. The agency has funded a great deal of very important stem cell medical research thats already produced terrific results and has the prospect of saving many more lives in the decade to come, he said.

Opponents include one member of the institutes board and a nonprofit that advocates for privacy in genetic research. They contend that the proposition seeks too much money and does not sufficiently address the conflicts of interest that cropped up after Prop. 71 was passed. They also note that private funding, including venture capital, for stem cell research has grown in recent years. Opponents had raised only $250 by late September, from a single contribution by the California Pro Life Council.

The editorial boards of some of Californias biggest newspapers also have opposed the measure, including the Los Angeles Times, the Orange County Register, the San Francisco Chronicle and the San Jose Mercury News/East Bay Times. The Fresno Bee, Modesto Bee, and San Luis Obispo Tribune newspaper editorial boards support Prop 14.

Jeff Sheehy, the only institute board member not to support Proposition 14, told CalMatters that the research environment has changed since voters initially approved state funding for stem cell research in 2004 and that California should prioritize other needs like education, health care, and housing.

I think the agencys done good work, but this was never planned to be funded forever with debt, Sheehy said. At this point the state cant afford it; were looking at a huge deficit.

Read the rest here:
Prop. 14: In the COVID age, can California still afford its stem cell research program? - CALmatters

Spinal Cord Stem Cells Comments Off on Prop. 14: In the COVID age, can California still afford its stem cell research program? – CALmatters | October 16th, 2020

By Michael Brown, CP Op-Ed Contributor | Thursday, October 15, 2020

Have you heard the latest? Trump cannot be pro-life since he used and is promoting the anti-COVID drug Regeneron, which was allegedly developed with the help of fetal tissue. And pro-life organizations are being hypocritical by refusing to condemn the drug. Is there any truth to these charges?

As reported by the UK Metro, Trump faces hypocrisy allegations after it was revealed Regeneron is made from stem cells originally taken from an embryonic kidney. That kidney was taken during an elective abortion performed in the Netherlands during the 1970s.

More bluntly, the MIT Technology Review claimed, Trumps antibody treatment was tested using cells originally derived from an abortion.

The Trump administration has looked to curtail research with fetal cells. But when it was life or death for the president, no one objected.

As for pro-life organizations, a lengthy headline on Business Insider stated, Antiabortion groups say they stand behind Trump's use of a drug tested on cells derived from an aborted fetus because the president was not involved with that abortion.

How should pro-life Trump voters respond to these concerns?

Lets say that Regeneron was actually developed with the help of fetal tissue. Does anyone actually think that doctors came to Trump and said, Mr. President, we have an experimental drug that was tested and developed using tissue from an aborted baby from the 1970s. How do you feel about using this?

Only the most hardened anti-Trumper could imagine such a scenario. In the world of reality, the very thought of it is absurd. And, even if the fetal tissue charges are true, who knew about this? Was this something that any of the doctors would have been aware of? I very seriously doubt it, especially when, as we shall see, Regeneron itself denies the charge.

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It is therefore completely ridiculous to claim that Trump is being hypocritical in using Regeneron, as if he knew the alleged history of the drug.

But that leads us back to the big question: Did Regeneron use fetal tissue from a baby aborted in the 1970s?

Another headline on Business Insider stated, One of Trump's COVID-19 treatments was developed using tissue that originally came from an abortion. He's tried to ban this kind of research.

This is being widely reported as established fact. But is it true?

In an official statement for the pro-life Charlotte Lozier Institute, David Prentice, Ph.D. and Tara Sander Lee, Ph.D., wrote:

The Regeneron therapy given to the president was made in Velocimmune humanized mice, a novel platform that uses genetically modifiedmouse embryonic stem (ES)cells to generate antibodies describedhereandhere.Development of Regenerons antibody cocktail is detailed in the journalScience, describing how they identified their antibodies made from Velocimmune miceandblood from recovered patientspreviously infected with SARS-CoV-2.The final antibody pair used in theREGN-COV2 therapycocktail was then produced inChinese hamster ovary (CHO) cells.Results from Regenerons REGN-COV2 clinical trials to treat COVID-19 patients are reportedhere.

Mouseembryonic stem cells and genetic modifications to make such mice date back to 1981, have been extensively studied, and were instrumental in the discovery of induced pluripotent stem (iPS) cells, another fully ethical alternative to fetal material, as discussed in thisNaturereview.iPSCs are much easier to use thanhuman embryonic stem cells,more flexible in their uses, and are not ethically controversial. No one has ever advocated against using mouse embryonic stem cells for development of therapies only against destruction of human lives.

In a statement made to The Christian Post, Alexandra Bowie, a spokesperson for Regeneron, explained, We did not use human stem cells or human embryonic stem cells in the development of REGN-COV2. We did use the HEK293T cell line to test our antibodies ability to neutralize the SARS-CoV-2 virus (they were used to make pseudovirus that looks like the Spike protein).

HEK293s are considered immortalized cells and are a common and widespread tool in research labs. The cell line was originally derived by adenovirus transformation of human embryonic kidney cells in 1977.

After this, it was further transformed at Stanford in the 80s with SV40 T-antigen (hence the T). HEK293T wasnt used in any other way and fetal tissue was not used in this research.

Im not a medical doctor or a scientist, but it seems clear from these descriptions (and from what I could glean from Regenerons technical article published in the journal Science, also cited above) that there is hardly a direct connection between the drug and an aborted baby.

Still, there is so much misinformation going viral online that Dr. Tara Lee started a Twitter account just to rebut the misconceptions. (Lees Twitter bio identifies her as Researcher, Clinical Scientist, Science Policy Advisor. PhD. Senior Fellow & Director of Life Sciences @lozierinstitute. For LIFE in this world and the next.)

She summarized the evidence in simple and clear terms: NO human embryonic stem cells or human fetal tissue were used to produce the treatments President Trump received period.

So, Regeneron denies that it used embryonic cells and other scientists deny it. This completely undermines the charge that pro-life groups are being hypocritical for not condemning the use of the drug (and the presidents promotion of it).

That being said, some pro-life groups have, in fact, opined that, even if testing for the drug could be traced back to an abortion in the 1970s, Trump had nothing to do with any of this and is therefore not being hypocritical in promoting the drug.

Is there some hypocrisy in this response?

Thats a fair question, and its the type of question that ethicists debate. If you could save the lives of many people using a drug that was developed with the help of aborted fetal cells, is that justifiable?

My answer to those accusing the president with hypocrisy is threefold. First, as stated here, its unlikely in the extreme he had any idea of the alleged abortion connection. Second, scientists from Regeneron deny any connection to human fetal cells, and Trump would presumably take them at their word. Third, if Regeneron had been developed with the help of an aborted baby, there would then be a serious ethical debate as to its use.

Still, with all that being said, it is grasping at straws to question the pro-life commitment of these organizations (along with that of President Trump). Thats because we are comparing the willful killing of more than 60 million babies in the womb, often out of convenience, with the possible, distant connection of a life-saving drug to a baby aborted in the 1970s. Who would seriously make such a comparison?

When it comes to the question of the benefit of embryonic cells in the development of medical cures, Dr. Lee noted that, Fetal tissue from aborted babies is not required for medical advancements. After 100+ years of research, no therapies have been developed that needed aborted fetal tissue to begin with. Newer & better ethical alternatives are available & being used now to make humanized mice.

There is, therefore, no justification for using embryonic fetus cells in medical research, and the Regeneron drug does not contradict this at all.

Of course, as readers here know well, I have no problem identifying President Trumps many, evident shortcomings, some of which can be quite destructive. And I continue to shake my head over some of the things he says.

But to call him a hypocrite or to question his pro-life commitment because he used Regeneron is to reveal ones anti-Trump animus. It indicts the accuser far more than it indicts the accused.

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Dr. Michael Brown(www.askdrbrown.org) is the host of the nationally syndicatedLine of Fireradio program. His latest book isEvangelicals at the Crossroads: Will We Pass the Trump Test?Connect with him onFacebook,Twitter, orYouTube.

Excerpt from:
Regeneron, Trump, and the alleged hypocrisy of the pro-life movement - Christian Post

IPS Cell Therapy Comments Off on Regeneron, Trump, and the alleged hypocrisy of the pro-life movement – Christian Post | October 16th, 2020

DUBLIN--(BUSINESS WIRE)--The "Cell Based Assay & High Content Screening Markets Market Forecasts by Application, With Executive and Consultant Guides and including Customized Forecasting and Analysis 2020 to 2024" report has been added to ResearchAndMarkets.com's offering.

This updated report will bring the entire management team up to speed, on both the technology and the opportunity.

Cell Based Assays are a mainstay of drug development and scientific research, but growth is now accelerating as new immuno-oncology markets create unprecedented investment in the race to cure cancer. On top of this new technology is allowing Cell Based Assays to be used to measure any aspect of cell function. This market just keeps on growing with no end in sight. The workhorse of the pharmaceutical industry is becoming a central player in biotechnology.

The technology is moving faster than the market. Genomics and Immunology are playing a role too. Find opportunities and pitfalls. Understand growth expectations and the ultimate potential market size.

Key Topics Covered:

1. Introduction and Market Definition

1.1 What are Cell Based Assays?

1.2 Clinical Trial Failures

1.2.1 Immuno-oncology Plays a Leading Role in Cell Based Assays

1.3 Market Definition

1.4 Methodology

1.5 U.S. Medical Market and Pharmaceutical Research Spending - Perspective

1.5.1 U.S. Expenditures for Pharmaceutical Research

2. Cell Based Assays - Guide to Technology

2.1 Cell Cultures

2.1.1 Cell Lines

2.1.2 Primary Cells

2.1.3 Stem Cells

2.1.3.1 iPSC's - The Special Case

2.2 Cell Assays

2.3 Cell Viability Assays

2.3 Cell Proliferation Assays

2.4 Cytotoxicity Assays

2.5 Cell Senescence Assays

2.6 Apoptosis

2.7 Autophagy

2.8 Necrosis

2.9 Oxidative Stress

2.10 2D vs. 3D

2.11 Signalling Pathways, GPCR

2.12 Immune Regulation & Inhibition

2.13 Reporter Gene Technology

2.14 CBA Design & Development

2.15 Cell Based Assays - The Takeaway

3. Industry Overview

3.1 Players in a Dynamic Market

3.1.1 Academic Research Lab

3.1.2 Contract Research Organization

3.1.3 Genomic Instrumentation Supplier

3.1.5 Cell Line and Reagent Supplier

3.1.6 Pharmaceutical Company

3.1.7 Audit Body

3.1.8 Certification Body

4. Market Trends

4.1 Factors Driving Growth

4.1.1 Candidate Growth

4.1.2 Immuno-oncology

4.1.3 Genomic Blizzard

4.1.4 Technology Convergence

4.1.5 The Insurance Effect

4.2 Factors Limiting Growth

4.2.1 CBA Development Challenges

4.2.2 Instrument Integration

4.2.3 Protocols

4.3 Technology Development

4.3.1 3D Assays

4.3.2 Automation

4.3.3 Software

4.3.4 Primary Cells

4.3.5 Signalling and Reporter Genes

4.3.6 The Next Five Years

5. Cell Based Assays Recent Developments

5.1 Recent Developments - Importance and How to Use This Section

5.1.1 Importance of These Developments

5.1.2 How to Use This Section

6. Profiles of Key Cell Based Assay Companies

7. Global Market Size

8. Global Market by User Type

8.1 Pharmaceutical Market

8.2 Basic Research Market

8.3 Industrial/Cosmetic Market

9. Cell Based Assay by Product Class

9.1 Instrument Market

9.2 Reagent Market

9.3 Services Market

9.4 Software Market

10. Appendices

10.1 FDA Cancer Drug Approvals by Year

10.2 Clinical Trials Started 2010 to 2016

10.3 Share of Pharma R&D by Country

For more information about this report visit https://www.researchandmarkets.com/r/1vziyy

Read the original:
Global Cell Based Assay & High Content Screening Markets to 2024: Updated Report - Understand Growth Expectations and the Potential Market Size -...

Cardiac Stem Cells Comments Off on Global Cell Based Assay & High Content Screening Markets to 2024: Updated Report – Understand Growth Expectations and the Potential Market Size -… | October 16th, 2020

Gosselies, Belgium, 14 October 2020, 7am CEST BONE THERAPEUTICS(Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today announces positive 24-month follow-up results for the Phase IIa study with the allogeneic cell therapy product, ALLOB, in patients undergoing lumbar spinal fusion procedures.

The 24-month data show a high percentage of successful lumbar vertebrae fusion of 90%. Patients also continue to experience important clinical improvements in function and pain, from as early as six months after treatment, up to the 24-month follow-up period.

Degenerative spine disorders have a major impact on the quality of life of patients. These impacts include decreases in the stability of the spine and pain in motion,said Dr. Alphonse Lubansu, M.D., Head of the Spinal Clinic, Erasme University Hospital, Universit libre de Bruxelles. The 24 month follow-up data of this Phase IIa clinical trial have demonstrated that patients treated with ALLOB in spinal fusion procedure show a high incidence in fusion, and benefit from a sustained, clinically meaningful improvement in function and pain throughout the 24 months following treatment together with a good safety profile. These results show that ALLOB in combination with the standard spine fusion surgery could be a promising treatment option to address the currently unmet needs of these patients.

This positive data forlumbar spinal fusion complementsthe strong Phase I/IIa results from ALLOB in patients with delayed union fractures,said Miguel Forte, MD, PhD, Chief Executive Officer of Bone Therapeutics. These studies provide promising clinical evidence for the potential ofBone Therapeuticsunique allogeneic cell therapy platform to address high unmet medical needs in orthopaedics and bone related disorders. We will now hold discussions with global regulators and our partners to explore a variety of options for the next stages of clinical development for ALLOB in different orthopedic indications, while pursuing the phase IIb study of ALLOB in difficult tibial fractures.In addition, theclinical results provide further evidence for the expansion of ALLOB and our platform of differentiated MSCs to other indications.

The multi-center, open-label proof-of-concept Phase IIa study was designed to evaluate the safety and efficacy of ALLOB administered, procedure in which an interbody cage with bioceramic granules mixed with ALLOB is implanted into the spine to achieve fusion of the lumbar vertebrae. The main endpoints of the 24-month follow-up analysis included safety and radiological assessments to evaluate vertebrae fusion (continuous bone bridges) and clinical assessments to evaluate improvement in patients functional disability as well as reduction in back and leg pain. The study evaluated 30 patients treated with ALLOB, 29 patients attended the 24-month visit.

Radiological data was collected from CT-scans at 24 months and assessed by three external readers. It showed a successful fusion of the lumbar vertebrae in 27 out of 30 patients (90%). In addition, the remaining 3 patients showed radiological evidence of bone formation. Treatment with ALLOB also resulted in a clear and statistically significant clinical improvement in function and reduction in pain over the 24-month follow-up period. Functional disability improved from the pre-treatment baseline to 24-month by a mean score of 60% (p<0.001) on the Oswestry Disability Index(1). Back and leg pain were strongly reduced by 57 to 62% (p<0.001) and 68 to 70% (p<0.001) respectively compared to pre-treatment baseline. Treatment with ALLOB was generally well-tolerated by the patients, consistent with previous reported results.

(1)The Oswestry Disability Index (ODI) is an index derived from the Oswestry Low Back Pain Questionnaire used by clinicians and researchers to measure a patients permanent functional disability. This validated questionnaire was first published by Jeremy Fairbank et al. in Physiotherapy in 1980. ODI score of 0%-20%: minimal disability; 21%-40%: moderate disability; 41%-60%: severe disability; 61%-80%: crippled; 81%-100%: bed bound.

About Spinal Fusion

Due to ageing populations and sedentary lifestyles, the number of people suffering from degenerative spine disorders continues to increase. Today, spinal fusion procedures are performed to relieve pain and improve patient daily functioning in a broad spectrum of degenerative spine disorders. Spinal fusion consists of bridging two or more vertebrae with the use of a cage and graft material, traditionally autologous bone graft or demineralised bone matrix placed into the intervertebral space for fusing an unstable portion of the spine and immobilizing a painful intervertebral motion segment. Over 1,000,000 spinal fusion procedures are performed annually in the US and EU, of which half at lumbar level and the market is growing at a rate of 5% per year. Although spinal fusion surgery is routine, non-fusion, slow progression to fusion and failure to eliminate pain are still frequent with up to 35% of patients not being satisfied with their surgery.

About ALLOB

ALLOB is the Companys off-the-shelf allogeneic cell therapy platform consisting of human allogeneic bone-forming cells derived from cultured bone marrow mesenchymal stem cells (MSC) from healthy adult donors, offering numerous advantages in product quality, injectable quantity, production, logistics and cost as compared to an autologous approach. To address critical factors for the development and commercialisation of cell therapy products, Bone Therapeutics has established a proprietary, optimised production process that improves consistency, scalability, cost effectiveness and ease of use of ALLOB. This optimized production process significantly increases the production yield, generating 100,000 of doses of ALLOB per bone marrow donation. Additionally, the final ALLOB product will be cryopreserved, enabling easy shipment and the capability to be stored in a frozen form at the hospital level. The process will therefore substantially reduce overall production costs, simplify supply chain logistics, improve patient accessibility and facilitate global commercialisation. The Company will implement the optimized production process for all future clinical trials with ALLOB.

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. The Company has a, diversified portfolio of cell and biologic therapies at different stages ranging from pre-clinical programs in immunomodulation to mid-to-late stage clinical development for orthopedic conditions, targeting markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf next-generation improved viscosupplement, JTA-004, which is currently in phase III development for the treatment of pain in knee osteoarthritis. Consisting of a unique combination of plasma proteins, hyaluronic acid a natural component of knee synovial fluid, and a fast-acting analgesic, JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain and inflammation. Positive phase IIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Currently in pre-clinical development, BT-20, the most recent product candidate from this technology, targets inflammatory conditions, while the 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 is ready to start 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 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 BioPark in Gosselies, Belgium. Further information is available atwww.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerJean-Luc Vandebroek, Chief Financial OfficerTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicCatherine HaquenneTel: +32 (0)497 75 63 56catherine@bepublic.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

For US Media and Investor Enquiries:LHA Investor RelationsYvonne BriggsTel: +1 310 691 7100ybriggs@lhai.com

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.

Originally posted here:
Bone Therapeutics' allogeneic cell therapy product, ALLOB, shows 90% fusion rate at 24 months in Phase IIa study in lumbar spinal fusion -...

Bone Marrow Stem Cells Comments Off on Bone Therapeutics’ allogeneic cell therapy product, ALLOB, shows 90% fusion rate at 24 months in Phase IIa study in lumbar spinal fusion -… | October 16th, 2020

Every 20 minutes someone in the UK is diagnosed with blood cancer and the register of stem cell donors who are needed to save thousands of patients lives does not currently meet the demand. Only 1 in 3 patients will find a donor match within their family and so every year over 2,000 people in the UK are left searching for a matching blood stem cell donor each year.

Blood cancer patients from Black, Asian or minority ethnicity groups face lower survival odds due to the lack ofdonordiversity. These patients have just a 20% chance of finding the best possible stem cell donor match, compared to 69% for northern European backgrounds.

This is due in part to the low numbers of donors registered from those Black, Asian or ethnic minority backgrounds. Donors from minority ethnic backgrounds make up just 13.1% of the UK stem cell register and because Black, Asian or ethnic minority patients tend to have more varied tissue meaning there is an even more specific biological requirement needed of a donor than for a white patient.

The global pandemic has made this situation even worse. Only 2% of stem cell registrations with DKMS came from black people during lockdown, falling by 20% compared to the same time the previous year.

Vaughn Scott is a patient who received a lifesaving donation from a stranger.

Vaughn Scott (34 years old) lives in Bristol and is grateful to the generous stranger who helped save his life. Theyve given him more time with his two children and the chance to marry his now wife last summer in a beautiful ceremony. Vaughn was incredibly fit and active, playing all kinds of sports and serving in the Navy. It was whilst on deployment across the world that he was urgently flown back to the UK and shockingly diagnosed with acute lymphoblastic leukaemia (ALL).

Vaughn said:

Hearing the diagnosis was the biggest blow Ive ever heard. My mind raced straight to my children and partner. When we learnt there was a way I could go into remission, I was excited that there was a way I could get better but very nervous too. With no family members as a match, all my faith was in a complete stranger that may have registered as a potential stem cell donor. Thankfully my match was found, Im now married and enjoying life with my family and Im so grateful. So many people arent as lucky as me. If you can, please register and give other people the second chance at life that I have been given.

To request a swab kit and register as a potential donor click HERE.

About blood cancer

Blood cancer is the third most common cause of cancer death in the UK but there is a lot of fear around stem cell donation of the process itself and of having a depleted supply of stem cells. This isnt the case. After donation, stem cells regenerate within 2 weeks so the donor wont lose anything. Blood stem cell donation is easy to do and similar to blood donation. Around 90% of all donations are made through a method called peripheral blood stem cell (PBSC). In this method, blood is taken from one of the donors arms and a machine extracts the blood stem cells from it. The donors blood is then returned to them through their other arm. This is an outpatient procedure that is usually completed in 4-6 hours. In just 10% of cases, donations are made through bone marrow collection. This is under general anaesthetic so that no pain is experienced.

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Black History Month The struggle to find a lifesaving stem cell donor - Keep the Faith

Bone Marrow Stem Cells Comments Off on Black History Month The struggle to find a lifesaving stem cell donor – Keep the Faith | October 16th, 2020

Indias first saviour sibling experiment is a success, say doctors.

A one-year-old sibling has saved her brothers life by donating her bone marrow. Kavya was conceived by her parents through invitro fertilisation to save her brother, Abhijeet Solanki, who was born with Thalassemia.

Thalassemia is a disorder where the haemoglobin count is low in blood and such persons require frequent blood transfusions.

Abhijeet was born in November 2013 but unlike normal babies he did not achieve the growth milestones. The parents learned that Abhijeet had Thalassemia major. Abhijeet required blood transfusions every 25 days and the gap between two transfusions reduced as he grew. By the age of six Abhijeet had undergone 80 transfusions, recalled his father Sahdev Singh Solanki. The only way to save him was through a bone marrow transplant.

The family was willing to donate their bone marrow but the human leukocyte antigen (HLA) of the family, including that of his older sister, did not match.

The Solanki family consulted many doctors. Mr. Solankis research led him to the saviour sibling concept following which he sought out Manish Banker, medical director of Nova IVF Fertility in Ahmedabad.

Dr. Banker said Mr. Solankis research and the science behind it was known but nobody had approached him with such a request before.

Dr. Banker started the assisted reproductive therapy, called pre-implantation genetic testing, for monogenic disorder with HLA matching. The couple underwent three cycles of IVF and 18 embryos were created. Of this only one perfectly matched Abhijeets HLA. The embryo was implanted in Apla Solanki, who delivered a baby girl a year ago.

We had to wait for the baby to grow. She had to weigh 10 kg before we could draw bone marrow, said Deepa Trivedi, programme director of Sankalp Bone Marrow Unit, CIMS Hospital, Ahmedabad.

Pointing out that the best therapeutic option for Thalassemia major patients is bone marrow transplant from an HLA-identical donor, Dr. Banker said, We are extremely thrilled to be part of reproductive history in India to create the first-ever saviour-sibling through ART. We used pre-genetic diagnosis and screening test, an established method for conceiving a child who may donate cord blood or hematopoietic stem cells for transplantation to save a critically ill sibling.

Mr. Solanki said the transplant was done on March 17. Since then Abhijeet has not needed any blood transfusion, indicating that he had been cured of the disorder. His haemoglobin count was 11.3, Dr. Trivedi said.

Read more:
A sister born to save ailing brother - The Hindu

Bone Marrow Stem Cells Comments Off on A sister born to save ailing brother – The Hindu | October 16th, 2020

Building on the transformative impetus from the first Food and Drug Administration (FDA)-approved Janus kinase (JAK) 1/2 inhibitor, ruxolitinib (Jakafi), in the clinical landscape of myeloproliferative neoplasms (MPNs), we are entering a new era of multiple JAK inhibitors and other diverse classes of drugs in rapid clinical development. Advancements in elucidating the pathophysiology of MPNs have spurred significant progress in developing novel promising agents or combination regimens with ruxolitinib to treat patients who are unresponsive to standard treatments or have specific clinical needs.

In myelofibrosis (MF), the most aggressive MPN, with an average survival of 5 to 7 years, abnormal clonal hematopoietic stem cell proliferation in the bone marrow (BM) leads to liberation of pro-inflammatory cytokines and extensive fibrosis, causing progressive pancytopenia, especially anemia and thrombocytopenia, along with splenomegaly and other symptoms, compromising quality of life.1

For nearly a decade, ruxolitinib has been the centerpiece therapy for patients with MF, markedly improving splenomegaly and constitutional symptoms and providing survival benefit.2 The second FDA-approved JAK2 inhibitor, fedratinib (Inrebic), may actually be a good second-line option for patients who are ruxolitinib-resistant with intermediate-2 and high-risk MF (primarily thrombocytopenic and characterized by platelet counts 50100 109/L).3 At present, 2 ongoing phase 3 clinical trials, the single-arm FREEDOM trial (NCT03755518) and the double-arm FREEDOM 2 trial (NCT03952039), are assessing the efficacy and safety of fedratinib in patients with MF who are resistant/refractory/intolerant to ruxolitinib. The FREEDOM trials are important because the previous JAKARTA studies (NCT01523171, NCT01437787) were placed on hold or terminated given concerns for the development of Wernicke encephalopathy. Pacritinib is a potent inhibitor of both JAK2 and fms-related receptor tyrosine kinase

3, or FLT3, but does not affect JAK1. Pacritinib is being evaluated in comparison with the physicians choice in an ongoing phase 3 trial (PACIFICA; NCT03165734) in patients with MF and severe thrombocytopenia (baseline platelet count < 50 109/L) at the optimal dose determined in the PAC203 study (200 mg twice daily; NCT03165734).3 Successful clinical development of pacritinib will provide a non-myelosuppressive JAK2 inhibitor for frontline treatment of patients with MF who have severe thrombocytopenia, a setting currently lacking approved drugs. Another JAK1/2 inhibitor that is in advanced clinical development and complements its predecessors is momelotinib, possessing the exclusive attribute to improve anemia, which becomes severe in patients with MF.3 At present, momelotinib is undergoing evaluation in patients who are symptomatic and anemic with advanced MF, previously treated with a JAK inhibitor, in a phase 3 trial (MOMENTUM; NCT04173494); the comparator drug is danazol.

Targeting anemia and thrombocytopenia. Given that patients with MF experience disease-associated and JAK inhibitor-induced anemia, several clinical trials have been evaluating drugs counteracting anemia, as monotherapies or in combination with ruxolitinib, in patients with MF-associated anemia.4 Currently, a global, multicenter phase 2 trial is under way to evaluate the safety and efficacy of luspatercept-aamt (Reblozyl), an activin receptor ligand trap that enhances late-stage erythropoiesis in patients with anemia and MF, including ruxolitinib-treated, transfusion-dependent individuals; a phase 3 trial (INDEPENDENCE) is planned for 2020. Interim results of the phase 2 study demonstrated significant efficacy of luspatercept-aamt, achieving reduction in red blood cell transfusion burden in ruxolitinib-treated patients with MF. Thalidomide (Thalomid), an immunomodulatory agent, significantly improved anemia and thrombocytopenia (platelet counts increased in 60% of patients) in a phase 2 trial evaluating ruxolitinib-treated patients with MF and baseline thrombocytopenia (NCT03069326).5

Synergistic combinations with ruxolitinib targeting epigenetics and JAK2 (TABLE). CPI-0610 is a selective bromodomain and extraterminal protein inhibitor that improved spleen volume, anemia, BM fibrosis, total symptom score, and transfusion dependence (alone or with ruxolitinib) in patients with MF who are enrolled in the global phase 2 MANIFEST study (NCT02158858).3 Furthermore, a phase 1 clinical trial combining an inhibitor of heat shock protein 90 (JAK2 is its chaperone protein), PU-H71, with ruxolitinib in patients with primary/secondary MF is under way (NCT03935555).3 The previous 2 trials are supported by preclinical data showing drug synergism. In a phase 2 trial of ruxolitinib/azacitidine (hypomethylating agent) in patients with MF, synergism was demonstrated in spleen length reduction and BM fibrosis improvement compared with ruxolitinib monotherapy (NCT01787487).5

Synergistic combinations with ruxolitinib targeting antiapoptotic proteins and JAK2. Navitoclax is an orally bioavailable inhibitor of the antiapoptotic B-cell lymphoma 2 (BCL2) family of proteins (primarily BCL extra-large [XL]). In preclinical studies, the nonclinical analogue of navitoclax, ABT-737, in combination with ruxolitinib showed synergism in inducing apoptosis of JAK2 V617F-driven MPN cell lines. Interim data from an ongoing phase 2 clinical trial evaluating navitoclax in combination with ruxolitinib in ruxolitinib-treated patients with MF (with baseline platelet count 100 109/L) showed reduction in spleen volume and BM fibrosis (1 grade) and improvement in total symptom score in a proportion of the patients (NCT03222609).3

Imetelstat is a short oligonucleotide telomerase inhibitor that possibly prolonged median overall survival in patients with MF in the higher-dose (9.4-mg/kg) arm of the phase 2 IMbark study (NCT02426086).3 A phase 3 trial comparing imetelstat to best available therapy in patients with refractory MF is planned for early 2021.

PRM-151, a plasma-derived analogue of the human antifibrotic protein pentraxin 2, improved BM fibrosis in mice models and patients with MF in preclinical and phase 1/2 clinical studies, respectively.3 The promising results merit a phase 3 trial, especially given the scarcity of antifibrotic agents.

The two relatively indolent MPN subtypes, polycythemia vera (PV) and essential thrombocythemia (ET), are characterized by abnorabnormal proliferation of myeloid cells, resulting in elevated blood counts (erythrocytosis and thrombocytosis in PV and ET, respectively), considerable risk of thrombosis and hemorrhage, and progression to secondary MF and acute myeloid leukemia (more common in PV than ET).6 In PV and ET, therapies are aimed at reducing risk of thrombosis, which is higher in patients over 60 years old or with a history of thrombosis, and in ET, when the calreticulin gene, CALR, is absent. A particularly promising agent for the two indolent MPNs is the long-acting ropeginterferon -2b, which was approved in Europe for frontline treatment of high-risk patients with PV and without symptomatic splenomegaly on the basis of the PROUD/CONTINUATION-PV studies [EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357- 17 (CONTINUATION-PV)].7 The previous investigations demonstrated superiority of ropeginterferon -2b versus hydroxyurea after 3 years of therapy. Besides awaiting possible approval of ropeginterferon -2b to treat patients with PV in the United States, a phase 3 trial of ropeginterferon -2b versus anagrelide in hydroxyurea-resistant/intolerant patients with ET has been planned to start in 2020. Givinostat, an inhibitor of histone deacetylases, demonstrated promising clinical responses (reduction in pruritus and thrombosis, and normalization of hematological parameters) in phase 1/2 studies in patients with JAK2 V617F positive PV and is entering a phase 3 trial in 2021.7 Currently, hydroxyurea and ruxolitinib are the first- and second-line treatments for high-risk patients with PV, respectively, and hydroxyurea is the first-line treatment for ET.

Herein we highlighted an array of drugs ranging from new JAK inhibitors to an antifibrotic agent, epigenetic modifiers, and telomerase and BCL-XL/BCL2 inhibitorsthat are in early or advanced clinical development in MPN. We are looking forward to enrichment of the MPN arsenal with new disease-modifying agents complementing the clinical benefits of ruxolitinib and fulfilling unmet needs in this population.

References:

1. Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156. doi:10.1186/s13045-017-0527-7

2. Bose P, Verstovsek S. Management of myelofibrosis after ruxolitinib failure. Leuk Lymphoma. Published online April 16, 2020. doi:10.1080/1 0428194.2020.1749606

3. Bose P, Verstovsek S. Management of myelofibrosis-related cytopenias. Curr Hematol Malig Rep. 2018;13(3):164-172. doi:10.1007/s11899- 018-0447-9

3. Bose P, Alfayez M, Verstovsek S. New concepts of treatment for patients with myelofibrosis. Curr Treat Options Oncol. 2019;20(1):5. doi:10.1007/s11864-019-0604-y

4. Bose P, Verstovsek S. Updates in the management of polycythemia vera and essential thrombocythemia. Ther Adv Hematol. 2019;10:2040620719870052. doi:10.1177/2040620719870052

5. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352- 3026(19)30236-4

6. Chifotides HT, Bose P, Verstovsek S. Givinostat: an emerging treatment for polycythemia vera. Expert Opin Investig Drugs. 2020;29(6):525- 536. doi:10.1080/13543784.2020.1761323

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New Therapies in Development for Myelofibrosis - Targeted Oncology

Bone Marrow Stem Cells Comments Off on New Therapies in Development for Myelofibrosis – Targeted Oncology | October 16th, 2020

Acute Lymphoblastic Leukemia (AML), also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, or acute nonlymphocytic leukemia, is an aggressive, fast-growing, heterogenous group of blood cancers that arise as a result of clonal expansion of myeloid hematopoietic precursors in the bone marrow. Not only are circulating leukemia (blast) cells seen in the peripheral blood, but granulocytopenia, anemia, and thrombocytopenia are also common as proliferating leukemia cells interfere with normal hematopoiesis.

Approximately 40-45% of younger and 10-20% of older adults diagnosed with AML are cured with current standard chemotherapy. However, the outlook for patients with relapsed and/or refractory disease is gloomy. Relapse following conventional chemotherapy remains is a major cause of death.

The process of manufacturing chimeric antigen receptor (CAR) T-cell therapies. [1] T-cells (represented by objects labeled as t) are removed from the patients blood. [2] Then in a lab setting the gene that encodes for the specific antigen receptors is incorporated into the T-cells. [3] Thus producing the CAR receptors (labeled as c) on the surface of the cells. [4] The newly modified T-cells are then further harvested and grown in the lab. [5]. After a certain time period, the engineered T-cells are infused back into the patient. This file is licensed by Reyasingh56 under the Creative Commons Attribution-Share Alike 4.0 International license.Today, the only curative treatment option for patients with AML is allogeneic hematopoietic stem cell transplantation or allo-HSCT, which through its graft-vs.-leukemia effects has the ability to eliminate residual leukemia cells. But it is an ption for only a minority. And despite a long history of success, relapse following allo-HSCT is still a major challenge and is associated with poor prognosis.

In recent years, rresearchers learned a lot about the genomic and epigenomic landscapes of AML. This understanding has paved the way for rational drug development as new drugable targets, resulting in treatments including the antibody-drug conjugate (ADC) gemtuzumab ozogamycin (Mylotarg; Pfizer/Wyeth-Ayerst Laboratories).

CAR T-cell TherapiesChimeric antigen receptor (CAR) T-cells therapies, using a patients own genetically modified T-cells to find and kill cancer, are one of the most exciting recent developments in cancer research and treatment.

Traditional CAR T-cell therapies are an autologous, highly personalised, approach in which T-cells are collected from the patient by leukopheresis and engineered in the laboratory to express a receptor directed at a cancer antigen such as CD19. The cells are then infused back into the patient after administration of a lymphodepletion regimen, most commonly a combination of fludarabine and cyclophosphamide. Durable remissions have been observed in pediatric patients with B-ALL and adults with NHL.

CD19-targeted CAR T-cell therapies, have, over the last decade, yielded remarkable clinical success in certain types of B-cell malignancies, and researchers have made substantial efforts aimed at translating this success to myeloid malignancies.

While complete ablation of CD19-expressing B cells, both cancerous and healthy, is clinically tolerated, the primary challenge limiting the use of CAR T-cells in myeloid malignancies is the absence of a dispensable antigen, as myeloid antigens are often co-expressed on normal hematopoietic stem/progenitor cells (HSPCs), depletion of which would lead to intolerable myeloablation.

A different approachBecause autologous CAR T-cell therapies are patient-specific, each treatment can only be used for that one patient. Furthermore, because CAR T-cells are derived from a single disease-specific antibody, they are, by design, only recognized by one specific antigen. As a consequence, only a small subset of patients with any given cancer may be suited for the treatment.

This specificity means that following leukopheresis, a lot of work needs to be done to create this hyper personalised treatment option, resulting in 3 5 weeks of manufacturing time.

The manufacturing process of CAR T-cell therapies, from a single academic center to a large-scale multi-site manufacturing center further creates challenges. Scaling out production means developing processes consistent across many collection, manufacturing, and treatment sites. This complexity results in a the realitively high cost of currently available CAR T-cell therapies.

To solve some of the concerns with currently available CAR T-cell therapies, researchers are investigating the option to develop allogenic, off-the-shelf Universal CAR T-cell (UCARTs) treatments that can be mass manufactured and be used for multiple patients.

Allogeneic CAR T-cell therapy are generally created from T-cells from healthy donors, not patients. Similar to the autologous approach, donor-derived cells are shipped to a manufacturing facility to be genetically engineered to express the antibody or CAR, however, in contrast to autologous CAR T-cells, allogeneic CAR T-cells are also engineered with an additional technology used to limit the potential for a graft versus host reaction when administered to patients different from the donor.

One unique benefit ofn this approach is that because these therapies hey are premade and available for infusion, there is no requirement to leukopheresis or a need to wait for the CAR T-cells to be manufactured. This strategy also will benefit patients who are cytopenic (which is not an uncommon scenario for leukemia patients) and from whom autologous T-cell collection is not possible.

PioneersAmong the pioneers of developing allogeneic CAR-T therapies are companies including Celyad Oncology, Cellectis, Allogene Therapeutics, and researchers at University of California, Los Angeles (UCLA) in colaboration with Kite/Gilead.

Researchers at UCLA were, for example, able to turn pluripotent stem cells into T-cells through structures called artificial thymic organoids. These organoids mimic the thymus, the organ where T-cells are made from blood stem cells in the body.

Celyad OncologyBelgium-based Celyad Oncology is advancing a number of both autologous and allogeneic CAR T-cell therapies, including proprietary, non-gene edited allogeneic CAR T-cell candidates underpinned by the companys shRNA technology platform. The shRNA platform coupled with Celyads all-in-one vector approach provides flexibility, versatility, and efficiency to the design of novel, off-the-shelf CAR T-cell candidates through a single step engineering process.

In July 2020, the company announced the start of Phase I trials with CYAD-211, Celyads first-in-class short hairpin RNA (shRNA)-based allogeneic CAR T candidate and second non-gene edited off-the-shelf program. CYAD-211 targets B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma and is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3 component of the T-cell receptor (TCR) complex.

During the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program in May 2020, the company presented updates from its allogeneic programs, including additional data from the alloSHRINK study, an open-label, dose-escalation Phase I trial assessing the safety and clinical activity of three consecutive administrations of CYAD-101, an investigational, non-gene edited, allogeneic CAR T-cell candidate engineered to co-express a chimeric antigen receptor based on NKG2D (a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM TCR Inhibitory Molecule), for the treatment of metastatic colorectal cancer (mCRC).

The expression of TIM reduces signalling of the TCR complex, which is responsible for graft-versus host disease.every two weeks administered concurrently with FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) in patients with refractory metastatic colorectal cancer (mCRC).

The safety and clinical activity data from the alloSHRINK trial in patients with mCRC demonstrated CYAD-101s differentiated profile as an allogeneic CAR T-cell candidate. Furthermore, the absence of clinical evidence of graft-versus-host-disease (GvHD) for CYAD-101 confirms the potential of non-gene edited approaches for the development of allogeneic CAR-T candidates.

Interim data from the alloSHRINK trial showed encouraging anti-tumor activity, with two patients achieving a confirmed partial response (cPR) according to RECIST 1.1 criteria, including one patient with a KRAS-mutation, the most common oncogenic alteration found in all human cancers. In addition, nine patients achieved stable disease (SD), with seven patients demonstrating disease stabilization lasting more than or equal to three months of duration.

Based on these results, clinical trials were broadened to include evaluating CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion as an expansion cohort of the alloSHRINK trial. Enrollment in the expansion cohort of the trial is expected to begin during the fourth quarter of 2020.

CellectisCellectis is developping a universal CAR T-cell (UCART) platform in an attempy to create off-the-shelf CAR T-cell therapies. The companys pipeline includes UCART123, a CAR T-cell therapy designed to targets CD123+ leukemic cells in acute myeloid leukemia (AML). The investigational agent is being studied in two open-label Phase I trials: AML123 studying the therapys safety and efficacy in an estimated 156 AML patients, and ABC123 studying the therapys safety and activity in an estimated 72 patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

UCART22Another investigational agent in clinical trials is UCART22 which is designed to treat both CD22+ B-cell acute lymphoblastic leukemia (B-ALL) and CD22+ B-cell non-Hodgkin lymphoma (NHL). Cellectis reported that UCART22 is included in an open-label, dose-escalating Phase I trial to study its safety and activity in relapsed or refractory CD22+ B-ALL patients.

UCART22 harbors a surface expression of an anti-CD22 CAR (CD22 scFv-41BB-CD3z) and the RQR8 ligand, a safety feature rendering the T-cells sensitive to the antibody rituximab. Further, to reduce the potential for alloreactivity, the cell surface expression of the T-cell receptor is abrogated through the inactivation of the TCR constant (TRAC) gene using Cellectis TALEN gene-editing technology.[1]

Preclinical data supporting the development of UCART22 was presented by Marina Konopleva, M.D., Ph.D. and her vteam during the 2017 annual meeting of the American Society of Hematology (ASH) meeting. [1]

Cellectis is also developing UCARTCS1 which is developed to treat CS1-expressing hematologic malignancies, such as multiple myeloma (MM). UCARTCLL1 is in preclinical development for treating CLL1-expressing hematologic malignancies, such as AML.

Cellectis and Allogene Therapeutics, another biotech company involved in the developmen t of CAR T-cell therapies, are developing ALLO-501, another CAR T-cell therapy which targets CD19 and is being developed for the the treatment of patients with relapsed or refractory NHL. Allogene Therapeutics is also developing ALLO-715, an investigational CAR T-cell therapy targeting the B-cell maturation antigen (BCMA) for treating relapsed or refractory multiple myeloma and ALLO-819, which targets CD135 (also called FLT3), for treating relapsed or refractory AML.

Allogene, in collaboration with both Cellectis, Pfizer (which has a 25% stake in Allogene) and Servier have numerous active open-label, single-arm Phase I trials for an off-the-shelf allogeneic CAR-T therapy UCART19* in patients with relapsed or refractory CD19+ B-ALL. Participating patients receive lymphodepletion with fludarabine and cyclophosphamide with alemtuzumab, followed by UCART19 infusion. Adults patients with R/R B-ALL are eligible.

The PALL aims to evaluate the safety and feasibility of UCART19 to induce molecular remission in pediatric patients with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) in 18 pediatric patients.

The CALM trial is a dose-escalating study evaluating the therapys safety and tolerability in 40 adult patients; and a long-term safety and efficacy follow-up study in 200 patients with advanced lymphoid malignancies.

Allogene reported preliminary proof-of-concept results during the annual meeting of the American Society of Hematology (ASH) in December 2018.

Data from the first 21 patients from both the PALL (n=7) and CALM (n=14) Phase I studies were pooled. The median age of the participating patients was 22 years (range, 0.8-62 years) and the median number of prior therapies was 4 (range, 1-6). Sixty-two percent of the patients (13/21) had a prior allogeneic stem cell transplant.

Of the 17 patients who received treatment with UCART19 and who received lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab, an anti-CD52 monoclonal antibody, 14 patients (82%) achieved CR/CRi, and 59% of them (10/17) achieved MRD-negative remission.

In stark contrast, the four patients who only received UCART19 and fludarabine and cyclophosphamide without alemtuzumab did not see a response and minimal UCART19 expansion.

Based on these results, researchers noted that apparent importance of an anti-CD52 antibody for the efficacy of allogeneic CAR-T therapies. In addition, safety data also looked promising. The trial results did not include grade 3 or 4 neurotoxicity and only 2 cases of grade 1 graft-versus-host disease (10%), 3 cases of grade 3 or 4 cytokine release syndrome which were considered manageable (14%), 5 cases of grade 3 or 4 viral infections (24%), and 6 cases of grade 4 prolonged cytopenia (29%).

Precision BiosciencesPrecision Biosciences is developing PBCAR0191, an off-the-shelf investigational allogeneic CAR T-cell candidate targeting CD19. The drug candidate is being investigated in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

The NHL cohort includes patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision has received both Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration (FDA).

A clinical trial with PBCAR0191 Precision Biosciences is exploring some novel lymphodepletion strategies in addition to fludarabine and cyclophosphamide. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well. This trial is enrolling patients.

In late September 2020, Precision BioSciences, a clinical stage biotechnology amd Servier, announced the companies have added two additional hematological cancer targets beyond CD19 and two solid tumor targets to its CAR T-cell development and commercial license agreement.

PBCAR20APBCAR20A is an investigational allogeneic anti-CD20 CAR T-cell therapy being developed by Precision Biosciences for the treartment of patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) and patients with R/R chronic lymphocytic leukemia (CLL) or R/R small lymphocytic lymphoma (SLL). The NHL cohort will include patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision BioSciences has received orphan drug designation from the United States Food and Drug Administration (FDA).

PBCAR20A is being evaluated in a Phase I/IIa multicenter, nonrandomized, open-label, dose-escalation and dose-expansion clinical trial in adult NHL and CLL/SLL patients. The trial will be conducted at multiple U.S. sites.

PBCAR269APrecision Biosciences is, in collaboration with Springworks Therapeutics, also developing PBCAR269A, an allogeneic BCMA-targeted CAR T-cell therapy candidate being evaluated for the safety and preliminary clinical activity in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study of adults with relapsed or refractory multiple myeloma. In this trial, the starting dose of PBCAR269A is 6 x 105 CAR T cells/kg body weight with subsequent cohorts receiving escalating doses to a maximum dose of 6 x 106 CAR T cells/kg body weight.

PBCAR269A is Precision Biosciencess third CAR T-cell candidate to advance to the clinic and is part of a pipeline of cell-phenotype optimized allogeneic CAR T-cell therapies derived from healthy donors and then modified via a simultaneous TCR knock-out and CAR T-cell knock-in step with the =companys proprietary ARCUS genome editing technology.

The FDA recently granted Fast Track Designation to PBCAR269A for the treatment of relapsed or refractory multiple myeloma for which the FDA previously granted Orphan Drug Designation.

TCR2 TherapeuticsTCR2 Therapeutics is developing a proprietary TRuC (TCR Fusion Construct) T-cells designed to harness the natural T cell receptor complex to recognize and kill cancer cells using the full power of T-cell signaling pathways independent of the human leukocyte antigen (HLA).

While succesful in hematological malignancies, CAR T-cells therapies have generally struggled to show efficacy against solid tumors. Researchers at TCR2 Therapeutics believe this is is caused by the fact that CAR T-cell therapies only utilize a single TCR subunit, and, as a result, do not benefit from all of the activation and regulatory elements of the natural TCR complex. By engineering TCR T-cells, which are designed to utilize the complete TCR, they have demonstrated clinical activity in solid tumors. However, this approach has also shown major limitations. TCR T-cells require tumors to express HLA to bind tumor antigens. HLA is often downregulated in cancers, preventing T-cell detection. In addition, each specific TCR-T cell therapy can only be used in patients with one of several specific HLA subtypes, limiting universal applicability of this approach and increasing the time and cost of patient enrollment in clinical trials.

In an attempt to solve this problem, researchers at TCR2 Therapeutics have developped a proprieatarry TRuC-T Cells which are designed to incorporate the best features of CAR-T and TCR-T cell therapies and overcome the limitations. The TRuC platform is a novel T cell therapy platform, which uses the complete TCR complex without the need for HLA matching.

By conjugating the tumor antigen binder to the TCR complex, the TRuC construct recognizes highly expressed surface antigens on tumor cells without the need for HLA and engage the complete TCR machinery to drive the totality of T-cell functions required for potent, modulated and durable tumor killing.

In preclinical studies, TCR2 Therapeutics TRuC T-cells technology has demonstrated superior anti-tumor activity in vivo compared to CAR T-cells therapies, while, at the same time, releasing lower levels of cytokines. These data are encouraging for the treatment of solid tumors where CAR T-cells have not shown significant clinical activity due to very short persistence and for hematologic tumors where a high incidence of severe cytokine release syndrome remains a major concern.

TCR2 Therapeutics product candidates include TC-210 and TC-110.

TC-210 is designed to targets mesothelin-positive solid tumors. While its expression in normal tissues is low, mesothelin is highly expressed in many solid tumors. Mesothelin overexpression has also been correlated with poorer prognosis in certain cancer types and plays a role in tumorigenesis. TC-210 is being developed for the treatment of non-small cell lung cancer, ovarian cancer, malignant pleural/peritoneal mesothelioma and cholangiocarcinoma.

The companys TRuC-T cell targeting CD19-positive B-cell hematological malignancies, TC-110, is being developed to improve upon and address the unmet needs of current CD19-directed CAR T-cell therapies. The clinical development TC-110 focus on the treatment of adult acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Preclinical data demonstrates that TC-110 is superior to CD19-CAR-T cells (carrying either 4-1BB or CD28 co-stimulatory domains) both in anti-tumor activity as well as the level of cytokine release which may translate into lower rates of adverse events. The development of TC-110 starts with autologous T-cells collection by leukopheresis. These T-cells undergo genetic engineering to create TRuC-T cells targeting CD19.

This strategy combines the best features of CAR T-cells and the native T-cell receptor. It is open for R/R NHL and R/R B-ALL.

AUTO1Auto1 is an autologous CD19 CAR T-cell investigational therapyis being developped by Autolus Therapeutics. The investigational drug uses a single-chain variable fragment (scFv) called CAT with a lower affinity for CD19 and a faster off-rate compared to the FMC63 scFv used in other approved CD19 CAR T-cell therapies. The investigational therapy is designed to overcome the limitations in safety while maintaining similar levels of efficacy compared to current CD19 CAR T-cell therapies.

Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T-cells, AUTO1 may reduce toxicity and be less prone to T-cell exhaustion, which could enhance persistence and improve the T-cells abilities to engage in serial killing of target cancer cells.

In 2018, Autolus signed a license agreement UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase I studies, one in pediatric ALL and one in adult ALL.

CARPALL trialInitial results from the ongoing Phase I CARPALL trial of AUTO1 were presented during European Hematology Association 1st European CAR T Cell Meeting held in Paris, France, February 14-16, 2019.

Enrolled patients had a median age of 9 years with a median of 4 lines of prior treatment. Seventeen patients were enrolled, and 14 patients received an infusion of CAR T cells. Ten of 14 patients had relapsed post allogeneic stem cell transplant. Eight patients were treated in second relapse, 5 in > second relapse and 3 had relapsed after prior blinatumomab or inotuzumab therapy. Two patients had ongoing CNS disease at enrollment.

This data confirmed that AUTO1 did not induces severe cytokine release syndrome (CRS) (Grade 3-5). Nine patients experienced Grade 1 CRS, and 4 patients experienced Grade 2 CRS. No patients required tociluzumab or steroids. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). The mean cumulative exposure to AUTO1 CAR T-cells in the first 28 days as assessed by AUC was 1,721,355 copies/g DNA. Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28: 3 patients Grades 1-3 and 8 patients Grade 4. Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR).

With a single dose of CAR T cells at 1 million cells/kg dose, 12/14 (86%) achieved molecular CR. Five patients relapsed with CD19 negative disease. Event free survival (EFS) based on morphological relapse was 67% (CI 34-86%) and 46% (CI 16-72%) and overall survival (OS) was 84% (CI 50-96%) and 63% (CI 27-85%) at 6 and 12 months, respectively.

CAR T cell expansion was observed in all responding patients (N=12), with CAR T cells comprising up to 84% of circulating T cells at the point of maximal expansion. The median persistence of CAR T-cells was 215 days.

The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Five of 14 patients (37%) remain in CR with ongoing persistence of CAR T-cells and associated B cell aplasia.

Fate TherapeuticsFT819 is an off-the-shelf CAR T-cell therapy targeting CD19 being developed by Fate Therapeutics. The T-cells are derived from a clonal engineered master induced pluripotent stem cell line (iPSCs) with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus and edited for elimination of T-cell receptor (TCR) expression.

Patients participating in the companys clinbical trial will receive lymphodepletion with fludarabine and cyclophosphamide. Some patients will also receive IL-2. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well.

At the Annual Meeting of the American Societ of Hematology held in December 2019, researchers from Fate Therapeutics presented new in vivo preclinical data demonstrating that FT819 exhibits durable tumor control and extended survival. In a stringent xenograft model of disseminated lymphoblastic leukemia, FT819 demonstrated enhanced tumor clearance and control of leukemia as compared to primary CAR19 T-cells. At Day 35 following administration, a bone marrow assessment showed that FT819 persisted and continued to demonstrate tumor clearance, whereas primary CAR T cells, while persisting, were not able to control tumor growth. [2]

CAR-NK CD19Allogeneic cord blood-derived Natural Killer (NK) cells are another off-the-shelf product that does not require the collection of cells from each patient.

Unlike T-cells, NK-cells do not cause GVHD and can be given safely in the allogeneic setting. At MD Anderson Cancer Center, Katy Rezvani, M.D., Ph.D, Professor, Stem Cell Transplantation and Cellular Therapy, and her team broadly focuses their research on the role of natural killer (NK) cells in mediating protection against hematologic malignancies and solid tumors and strategies to enhance killing function against various cancer.

As part of their research, the team has developed a novel cord blood-derived NK-CAR product that expresses a CAR against CD19; ectopically produces IL-15 to support NK-cell proliferation and persistence in vivo; and expresses a suicide gene, inducible caspase 9, to address any potential safety concerns.

In this phase I and II trial researchers administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkins lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1105, 1106, or 1107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. The preliminarry resilts of the trials confirmed that administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline.

The study results also demonstrated that of the 11 patients who were treated, 8 patients (73%) had a response. Of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission ICR), and 1 had remission of the Richters transformation component but had persistent CLL. Noteworthy was that responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. The researchers also noted that a majority of the 11 participating patients with relapsed or refractory CD19-positive cancers had a response to treatment with CAR-NK cells without the development of major toxic effects.[3]

Note* Servier will hold ex-US commercial rights. Servier is the sponsor of the UCART19 trials.

Clinical trialsalloSHRINK Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells NCT03692429Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (AMELI-01) NCT03190278Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN (ABC123) NCT03203369Study of UCART19 in Pediatric Patients With Relapsed/Refractory B Acute Lymphoblastic Leukemia (PALL) NCT02808442Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia (CALM) NCT02746952Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL NCT03666000.Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL NCT04030195A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A in Study Participants With Relapsed/Refractory Multiple Myeloma NCT04171843TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia NCT04323657Phase 1/2 Trial of TC-210 T Cells in Patients With Advanced Mesothelin-Expressing Cancer NCT03907852CARPALL: Immunotherapy With CD19 CAR T-cells for CD19+ Haematological Malignancies NCT02443831Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies NCT03056339

Reference[1] Petti F. Broadening the Applicability of CAR-T Immunotherapy to Treat the Untreatable. OncoZine. October 24, 2019 [Article][2] Wells J, Cai T, Schiffer-Manniou C, Filipe S, Gouble A, Galetto R, Jain N, Jabbour EJ, Smith J, Konopleva M. Pre-Clinical Activity of Allogeneic Anti-CD22 CAR-T Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia Blood (2017) 130 (Supplement 1): 808. https://doi.org/10.1182/blood.V130.Suppl_1.808.808%5B3%5D Chang C, Van Der Stegen S, Mili M, Clarke R, Lai YS, Witty A, Lindenbergh P, Yang BH, et al. FT819: Translation of Off-the-Shelf TCR-Less Trac-1XX CAR-T Cells in Support of First-of-Kind Phase I Clinical Trial. Blood (2019) 134 (Supplement_1): 4434.https://doi.org/10.1182/blood-2019-130584%5B4%5D Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607. PMID: 32023374; PMCID: PMC7101242.

Featured image: T-cells attacking a cancer cell. Photo courtesy: Fotolia/Adobe 2016 2020. Used with permission.

Link:
CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia - OncoZine

Bone Marrow Stem Cells Comments Off on CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia – OncoZine | October 16th, 2020

NEW YORK, Oct. 15, 2020 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

Conference Call & WebcastThursday, October 15, 2020 at 8 a.m. Eastern TimeFrom the US: 877-407-9205International: 201-689-8054Webcast: https://www.webcaster4.com/Webcast/Page/2354/37811

Replays, available through October 29, 2020From the US: 877-481-4010International: 919-882-2331Replay Passcode: 37811

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment in August 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment in August 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, regulatory approval of BrainStorm's NurOwn treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

ContactsInvestor Relations:Corey Davis, Ph.D.LifeSci Advisors, LLCPhone: +1 646-465-1138cdavis@lifesciadvisors.com

Media:Paul TyahlaSmithSolvePhone: + 1.973.713.3768Paul.tyahla@smithsolve.com

BRAINSTORM CELL THERAPEUTICS INC. AND SUBSIDIARIESINTERIM CONDENSED CONSOLIDATED BALANCE SHEETSU.S. dollars in thousands(Except share data)

September 30,

December 31,

2020

2019

U.S. $ in thousands

Unaudited

Audited

ASSETS

Current Assets:

Cash and cash equivalents

$

24,770

$

536

Short-term deposit (Note 4)

4,038

33

Other accounts receivable

1,473

2,359

Prepaid expenses and other current assets (Note 5)

56

432

Total current assets

30,337

3,360

Long-Term Assets:

Prepaid expenses and other long-term assets

27

32

Operating lease right of use asset (Note 6)

1,377

2,182

Property and Equipment, Net

950

960

Total Long-Term Assets

2,354

3,174

Total assets

$

32,691

$

6,534

LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIT)

Current Liabilities:

Accounts payable

$

3,283

$

14,677

Accrued expenses

917

1,000

Operating lease liability (Note 6)

1,216

1,263

Other accounts payable

1,013

714

Total current liabilities

6,429

17,654

Long-Term Liabilities:

Operating lease liability (Note 6)

284

1,103

Total long-term liabilities

284

1,103

Total liabilities

$

6,713

$

18,757

Stockholders' Equity (deficit):

Stock capital: (Note 7)

12

11

Common Stock of $0.00005 par value - Authorized: 100,000,000 shares at September 30, 2020 and December 31, 2019 respectively; Issued and outstanding: 31,567,592 and 23,174,228 shares at September 30, 2020 and December 31, 2019 respectively.

Additional paid-in-capital

View post:
BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update - BioSpace

Bone Marrow Stem Cells Comments Off on BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update – BioSpace | October 16th, 2020

BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment in August 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment in August 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

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BrainStorm Announces Financial Results for the Third Quarter 2020 - Citybizlist

Bone Marrow Stem Cells Comments Off on BrainStorm Announces Financial Results for the Third Quarter 2020 – Citybizlist | October 16th, 2020

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An international team of researchers has published a study showing how the control of stem cell metabolism is critical to maintaining hair follicles. The study appeared in the high-impact journal Cell Metabolism.

University of Arkansas researchers included Kyle Quinn, associate professor of biomedical engineering, and Olivia Kolenc, a graduate student in Quinn's lab. The project was led by Sara Wickstrm, associate professor at the University of Helsinki, and included researchers from the research groups of Professor Sabine Eming at the University of Cologne and Martin Denzel at the Max Planck Institute for Biology of Ageing in Germany.

The team studied how the metabolism of stem cells in hair follicles is critical to the growth and long-term maintenance of hair. The follicles are unique in mammals because unlike most organs or tissues, they naturally regenerate and cycle through phases of rest, growth and degeneration. Those cycles are maintained by stem cells. Kolenc used advanced non-invasive skin imaging to monitor hair follicle metabolism in live mice.

Kolenc's work showed how the metabolism of stem cells changes as the follicle transitions to a growth phase, which provided a critical foundation to the study's larger goal of discovering the cell signaling pathways associated with the metabolic control of stem cell fate and hair follicle cycles.

The study provides insight into how our organs are maintained by stem cells and how aging can result in conditions such as hair loss. Kolenc said hair follicle stem cells aren't like some stem cells, which can transform into a wide variety of different cell types. Instead, she said, they can transform to match the surrounding area in the skin tissue.

"Hair follicle stem cells are able to differentiate into a subset of what's in their surrounding area," she said. "They can't just create any other cell, but they can contribute to regeneration and increasing the number of cells within the skin tissue."

Kolenc said hair follicle stem cells are unique among the cells in our skin because they can contribute to repair and regeneration of the skin.

"There are few populations of stem cells known to exist within the skin, so this is really a big target to help skin wound healing," she said.

Kolenc said the opportunity to contribute to such a large-scale project was special.

"It's a bit humbling," she said. "I contributed a small part to a large project that was conducted over many years. It's a cool feeling to see something like that with my name on it."

"Olivia played an important role in this study by monitoring hair follicle stem cells within their natural environment in live skin," Quinn said. "The insights she gained during this work will be very helpful as she continues studying how our metabolic imaging techniques can be applied to aging and wound healing research."

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Biomedical Engineering Team Contributes to High-impact Study on Metabolism - University of Arkansas Newswire

Skin Stem Cells Comments Off on Biomedical Engineering Team Contributes to High-impact Study on Metabolism – University of Arkansas Newswire | October 16th, 2020

Vanderbilt University researchers have reported the counterintuitive discovery that certain chemotherapeutic agents used to treat tumors can have the opposite effect of tissue overgrowth in normal, intact mammary glands, epidermis and hair follicles. The researchers also are the first to report the discovery of an innate immune signaling pathway in fibroblaststhe spindle-shaped cells responsible for wound healing and collagen productionthat causes cells to proliferate. Such signaling pathways previously were attributed only to immune cells.

The article describing the research, DNA Damage Promotes Epithelial Hyperplasia and Fate Mis-specification via Fibroblast Inflammasome Activation, was published in the journal Developmental Cell on Oct. 13.

The findings of this work, led by postdoctoral fellow Lindsey Seldin and Professor and Chair of the Department of Cell and Developmental Biology Ian Macara, have broad implications for diseases associated with the immune system like psoriasis, as well as cancer and stem cell research.

Understanding the functionality of stem cells and the way that their behavior is regulated has been a longstanding research interest for Seldin. Normal stem cells have an amazing ability to continuously divide to maintain tissue function without forming tumors, she explained. We wanted to understand what happens to these cells in their native environment when subjected to damage, and if the response was connected to a specific tissue.

By testing perturbations to the epidermis, mammary gland and hair follicles vis--vis mechanical damage or DNA damage through chemotherapeutic agents, the researchers saw a paradoxical response: Stem cells, which otherwise would divide slowly, instead divided rapidly, promoting tissue overgrowth.

When the tissues were subjected to DNA damage, their stem cells overly proliferated, giving rise to different cells than they normally would. This was a very perplexing result, said Seldin, the papers lead author. We were determined to figure out if this was a direct response by the stem cells themselves or by inductive signals within their environment. The key clue was that stem cells isolated from the body did not behave the same way as in intact tissuean indication that the response must be provoked from signals being sent to the stem cells from other surrounding cell types.

The investigators turned their attention to fibroblasts, the predominant component of the tissue microenvironment. When fibroblasts in the epidermis were removed, the stem cell responsiveness to DNA damage was diminished, indicating that they played an important role. RNA sequencing revealed that fibroblasts can signal by way of inflammasomescomplexes within cells that help tissues respond to stress by clearing damaged cells or pathogens, which also in this case caused stem cells to divide. This is an astounding discovery, said Macara. Inflammasome signaling has previously been attributed only to immune cells, but now it seems that fibroblasts can assume an immune-like nature.

Seldin intends to replicate this work in the mammary gland to determine whether fibroblasts initiate the same innate immune response as in the epidermis, and more broadly how fibroblasts contribute to the development of cancer and other diseases associated with the immune system.

This work was supported by NCI/NIH grants R35CA132898, F32CA213794 and T32CA119925, as well as American Cancer Society grant PF-18-007-01-CCG.

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Vanderbilt researchers make counterintuitive discoveries about immune-like characteristics of cells, chemotherapys impact on tissue growth -...

Skin Stem Cells Comments Off on Vanderbilt researchers make counterintuitive discoveries about immune-like characteristics of cells, chemotherapys impact on tissue growth -… | October 16th, 2020

HAIFA, Israel, Oct. 13, 2020 (GLOBE NEWSWIRE) -- Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PSTI), a leading regenerative medicine company developing a platform of novel biological products, today announced that it has received clearance from the safety committee of an investigator initiated Phase I/II study to move forward with patient enrollment for cohort II. The study will evaluate PLX-PAD cells in the treatment of steroid-refractory chronic graft vs. host disease (GvHD) and is led by Principal Investigator Prof. Ron Ram, Director of the Hematology Blood and Marrow Stem Cell Transplantation Unit at Tel Aviv Sourasky Medical Center, Ichilov Hospital, Israel. Prof. Ram and his research staff are responsible for the design and implementation of the study at Sourasky Medical Center.

GvHD is a severe complication in patients who have undergone an allogeneic hematopoietic cell transplantation (HCT) and is a major cause of morbidity and mortality in these patients in which the donated stem cells identify the recipient's body as foreign and attack it. The chronic form of GvHD (cGvHD) usually appears later than 100 days post-transplant.

Cohort I included 6 patients treated with 2 injections of 150 million cells, a week apart. At the 3-month follow up, interim safety results concluded that PLX-PAD cells were safe and that no treatment related side effects were reported. Efficacy results demonstrated that 4 out of the 6 patients reported improvement in symptoms that translated into a reduction in the severity of cGvHD with notable reduction in the required steroid doses for part of the patients. Based on these results, the study was approved to commence enrollment of 14 patients in cohort II to be treated with 4 injections of 150 million cells.

Prof. Ram of Ichilov Hospital commented, From our experience in having treated 6 patients in the study to date, we have so far found no negative side effects from the use of the PLX-PAD cells in the treatment of steroid-refractory cGvHD. Patients with significant GvHD skin disorders previously unresponsive to multiple types of therapy showed remarkable response. Responses were also observed for severe mouth ulcers which prevented patients from eating solid foods. This resulted in a major improvement of quality of life and tapering of steroid doses."

Pluristem is committed to contributing to the wellbeing and quality of life of our patients. cGvHD is an indication where we see a significant need to enhance the current course of treatment for this life-threatening condition among patients undergoing bone marrow transplants. The preliminary results from cohort I of this Phase I/II study, and prior preclinical data, both indicate that PLX-PAD cells may potentially treat cGvHD patients and mitigate symptoms. We are very pleased to cooperate with Prof. Ram and Sourasky Medical Center, and we place a high importance in examining PLX-PAD for this indication, stated Pluristem CEO and President, Yaky Yanay.

About cGvHDChronic graft-versus-host disease (cGvHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GvHD requiring systemic treatment is 30% to 40% by National Institutes of Health criteria1. The hematopoietic stem cell transplants are used to treat bone marrow failure resulting from treatment of some blood or bone marrow cancers as well as other hematologic failures, such as aplastic anemia, which are not related to cancer. The donated cells identify the recipients body as foreign and attack it as a result. While acute GvHD usually appears in the first 100 days after a transplant, and in specific body systems, chronic GvHD can occur at any time (even several years) after a transplant, and may manifest in many parts of the body such as: skin, mouth, eyes, liver, intestines, lungs and joints. Long term immunosuppression is given to try to prevent or treat cGvHD. Since this treatment suppresses the immune system for a very long time, patients are at high risk of infections, and are prescribed multiple medications to try to address this major risk.

About Pluristem TherapeuticsPluristem Therapeutics Inc. is a leading regenerative medicine company developing novel placenta-based cell therapy product candidates. The Company has reported robust clinical trial data in multiple indications for its patented PLX cell product candidates and is currently conducting late stage clinical trials in several indications. PLX cell product candidates are believed to release a range of therapeutic proteins in response to inflammation, ischemia, muscle trauma, hematological disorders and radiation damage. The cells are grown using the Company's proprietary three-dimensional expansion technology and can be administered to patients off-the-shelf, without tissue matching. Pluristem has a strong intellectual property position; a Company-owned and operated GMP-certified manufacturing and research facility; strategic relationships with major research institutions; and a seasoned management team.

Safe Harbor StatementThis press release contains express or implied forward-looking statements within the Private Securities Litigation Reform Act of 1995 and other U.S. Federal securities laws. For example, Pluristem is using forward-looking statements when it discusses the patient enrollment for cohort II for its Phase I/II study of its PLX-PAD cells, the implication from the results of the first patient cohort in the study, the belief that GvHD is an indication that has a significant need for enhanced treatments among patients undergoing bone marrow transplants and that the preliminary results from cohort I of the study, and the prior preclinical data, indicate that PLX-PAD cells may potentially treat chronic GvHD patients and mitigate symptoms. These forward-looking statements and their implications are based on the current expectations of the management of Pluristem only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; Pluristem may encounter delays or obstacles in launching and/or successfully completing its clinical trials; Pluristems products may not be approved by regulatory agencies, Pluristems technology may not be validated as it progresses further and its methods may not be accepted by the scientific community; Pluristem may be unable to retain or attract key employees whose knowledge is essential to the development of its products; unforeseen scientific difficulties may develop with Pluristems process; Pluristems products may wind up being more expensive than it anticipates; results in the laboratory may not translate to equally good results in real clinical settings; results of preclinical studies may not correlate with the results of human clinical trials; Pluristems patents may not be sufficient; Pluristems products may harm recipients; changes in legislation may adversely impact Pluristem; inability to timely develop and introduce new technologies, products and applications; loss of market share and pressure on pricing resulting from competition, which could cause the actual results or performance of Pluristem to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, Pluristem undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed description of the risks and uncertainties affecting Pluristem, reference is made to Pluristem's reports filed from time to time with the Securities and Exchange Commission.

Contact:

Dana RubinDirector of Investor Relations972-74-7107194danar@pluristem.com

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1 Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015 Jan 22;125(4):606-15. doi: 10.1182/blood-2014-08-551994. Epub 2014 Nov 14. PMID: 25398933; PMCID: PMC4304105., https://pubmed.ncbi.nlm.nih.gov/25398933/

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Pluristem Announces Clearance to Move Forward with Enrollment for Cohort II in an Investigator-Led Phase I/II Chronic Graft vs Host Disease...

Skin Stem Cells Comments Off on Pluristem Announces Clearance to Move Forward with Enrollment for Cohort II in an Investigator-Led Phase I/II Chronic Graft vs Host Disease… | October 16th, 2020