Stem cell-derived blood-brain barrier gives more complete picture of Huntington’s disease

Like a sophisticated security fence, our bodies have evolved a barrier that protects the brain from potentially harmful substances in the blood but still allows the entry of essential molecules like blood sugar and oxygen. Just like in other parts of the body, the blood vessels and capillaries in the brain are lined with endothelial cells. But in the brain, these cells form extremely tight connections with each other making it nearly impossible for most things to passively squeeze through the blood vessel wall and into the brain fluid.

BloodBrainBarrier

Compared to blood vessels in other parts of the body, brain blood vessels form a much tighter seal to protect the brain.
Image source: Dana and Chris Reeve Foundation

Recent studies have shown defects in the brain-blood barrier are associated with neurodegenerative disorders like Huntington’s disease and as a result becomes leakier. Although the debilitating symptoms of Huntington’s disease – which include involuntary movements, severe mood swings and difficulty swallowing – are primarily due to the gradual death of specific nerve cells, this breakdown in the blood-brain barrier most likely contributes to the deterioration of the Huntington’s brain.

What hasn’t been clear is if mutations in Huntingtin, the gene that is linked to Huntington’s disease, directly impact the specialized endothelial cells within the blood-brain barrier or if these specialized cells are just innocent bystanders of the destruction that occurs as Huntington’s progresses. It’s an important question to answer. If the mutations in Huntingtin directly affect the blood-brain barrier then it could provide a bigger picture of how this incurable, fatal disease works. More importantly, it may provide new avenues for therapy development.

A UC Irvine research team got to the bottom of this question with the help of induced pluripotent stem cells (iPSCs) derived from the skin cells of individuals with Huntington’s disease. Their CIRM-funded study was published this week in Cell Reports.

In a first for a neurodegenerative disease, the researchers coaxed the Huntington’s disease iPSCs in a lab dish to become brain microvascular endothelial cells (BMECs), the specialized cells responsible for forming the blood-brain barrier. The researchers found that the Huntington’s BMECs themselves were indeed dysfunctional. Compared to BMECs derived from unaffected individuals, the Huntington’s BMECs weren’t as good at making new blood vessels, and the vessels they did make were leakier. So the Huntingtin mutation in these BMECs appears to be directly responsible for the faulty blood-brain barrier.

The team dug deeper into this new insight by looking for possible differences in gene activity between the healthy and Huntington’s BMECs. They found that the Wnt group of genes, which plays an important role in the development of the blood-brain barrier, are over active in the Huntington’s BMECs. This altered Wnt activity can explain the leaky defects. In fact, the use of a drug inhibitor of Wnt fixed the defects. Dr. Leslie Thompson, the team lead, described the significance of this finding in a press release:

“Now we know there are internal problems with blood vessels in the brain. This discovery can be used for possible future treatments to seal the leaky blood vessels themselves and to evaluate drug delivery to patients with HD.”

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Study leader, Leslie Thompson. Steve Zylius / UCI

A companion Cell Stem Cell report, also published this week, used the same iPSC-derived blood-brain barrier system. In that study, researchers at Cedars-Sinai pinpointed BMEC defects as the underlying cause of Allan-Herndon-Dudley syndrome, another neurologic condition that causes mental deficits and movement problems. Together these results really drive home the importance of studying the blood-brain barrier function in neurodegenerative disease.

Dr. Ryan Lim, the first author on the UC Irvine study, also points to a larger perspective on the implications of this work:

“These studies together demonstrate the incredible power of iPSCs to help us more fully understand human disease and identify the underlying causes of cellular processes that are altered.”

Bridging the Gap: Regenerating Injured Bones with Stem Cells and Gene Therapy

Scientists from Cedars-Sinai Medical Center have developed a new stem cell-based technology in animals that mends broken bones that can’t regenerate on their own. Their research was published today in the journal Science Translational Medicine and was funded in part by a CIRM Early Translational Award.

Over two million bone grafts are conducted every year to treat bone fractures caused by accidents, trauma, cancer and disease. In cases where the fractures are small, bone can repair itself and heal the injury. In other cases, the fractures are too wide and grafts are required to replace the missing bone.

It sounds simple, but the bone grafting procedure is far from it and can cause serious problems including graft failure and infection. People that opt to use their own bone (usually from their pelvis) to repair a bone injury can experience intense pain, prolonged recovery time and are at risk for nerve injury and bone instability.

The Cedars-Sinai team is attempting to “bridge the gap” for people with severe bone injuries with an alternative technology that could replace the need for bone grafts. Their strategy combines “an engineering approach with a biological approach to advance regenerative engineering” explained co-senior author Dr. Dan Gazit in a news release.

Gazit’s team developed a biological scaffold composed of a protein called collagen, which is a major component of bone. They implanted these scaffolds into pigs with fractured leg bones by inserting the collagen into the gap created by the bone fracture. Over a two-week period, mesenchymal stem cells from the animal were recruited into the collagen scaffolds.

To ensure that these stem cells generated new bone, the team used a combination of ultrasound and gene therapy to stimulate the stem cells in the collagen scaffolds to repair the bone fractures. Ultrasound pulses, or high frequency sound waves undetectable by the human ear, temporarily created small holes in the cell membranes allowing the delivery of the gene therapy-containing microbubbles into the stem cells.

Image courtesy of Gazit Group/Cedars-Sinai.

Animals that received the collagen transplant and ultrasound gene therapy repaired their fractured leg bones within two months. The strength of the newly regenerated bone was comparable to successfully transplanted bone grafts.

Dr. Gadi Pelled, the other senior author on this study, explained the significance of their research findings for treating bone injuries in humans,

“This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat non-healing bone fractures. It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.”

You can learn more about this study by watching this research video provided by the Gazit Group at Cedars-Sinai.


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UCSD scientists devise tiny sensors that detect forces at cellular level

A big focus of stem cell research is trying to figure how to make a stem cell specialize, or differentiate, into a desired cell type like muscle, liver or bone. When we write about these efforts in the Stem Cellar, it’s usually in terms of researchers identifying proteins that bind to a stem cell’s surface and trigger changes in gene activity inside the cell that ultimately leads to a specific cell fate.

But, that’s not the only game in town. As incredible as it sounds, affecting a cell’s shape through mechanical forces also plays a profound role in gene activity and determining a cell’s fate. In one study, mesenchymal stem cells would specialize into fat cells or bone-forming cells depending on how much the MSCs were stretched out on a petri dish.

An artist’s illustration of nano optical fibers detecting the minuscule forces produced by swimming bacteria. Credit: Rhett S. Miller/UC Regents

Since we’re talking about individual cells, the strength of these mechanical forces is tiny, making measurements nearly impossible. But now, a research team at UC San Diego has engineered a device 100 times thinner than a human hair that can detect these miniscule forces. The study, funded in part by CIRM, was reported yesterday in Nature Photonics.

The device is made of a very thin optical fiber that’s coated with a resin which contains gold particles. The fiber is placed directly into the liquid that cells are grown in and then hit with a beam of light. The light is scattered by the gold particles and measured with a conventional light microscope. Forces and even sound waves caused by cells in the petri dish change the intensity of the light scattering which is detected by the microscope.

Donald Sirbuly,
team lead

In this study, the researchers measured astonishingly small forces (0.0000000000001 pound of force, to be exact!) in a culture of gut bacteria which swim around in the solution with the help of their whip-like flagella. The team also detected the sound of beating heart muscle cells at a level that’s a thousand times below the range of human hearing.

Dr. Donald Sirbuly, the team lead and a professor at UCSD’s Jacobs School of Engineering is excited about the research possibilities with this device:

“This work could open up new doors to track small interactions and changes that couldn’t be tracked before,” he said in a press release.

Bradley Fikes, the biotechnology reporter for the San Diego Union Tribune, reached out to others in the field to get their take on potential applications of this nanofiber device. Dr. John Marohn at Columbia University told Fikes in a news article (subscription is needed to access) that it could help stem cell scientists’ fully understand all of the intricacies of cell fate:

“So one of the cues that cells get, and they listen to these cues to decide how to change how to evolve, are just outside forces. This would give a way to kind of feel the outside forces that the cells feel, in a noninvasive way.”

And Eli Rothenberg at NYU School of Medicine, also not part of the study, summed up the device’s novelty, power and ease of use in an interview with Fikes:

“One of the main challenges in measuring things in biology is forces. We have no idea what’s going on in terms of forces in cells, in term of motion of molecules, the forces they interact with. But these sensors, you can put anywhere. They’re tiny, you can place them on the cells. If a cancer cell’s surface is moving, you can measure the forces…The fabrication of this device is quite straightforward. So, the simplicity of having this device and what you can measure with it, that’s kind of striking.”

 

 

Positively good news from Asterias for CIRM-funded stem cell clinical trial for spinal cord injury

AsteriasWhenever I give a talk on stem cells one of the questions I invariably get asked is “how do you know the cells are going where you want them to and doing what you want them to?”

The answer is pretty simple: you look. That’s what Asterias Biotherapeutics did in their clinical trial to treat people with spinal cord injuries. They used magnetic resonance imaging (MRI) scans to see what was happening at the injury site; and what they saw was very encouraging.

Asterias is transplanting what they call AST-OPC1 cells into patients who have suffered recent injuries that have left them paralyzed from the neck down.  AST-OPC1 are oligodendrocyte progenitor cells, which develop into cells that support and protect nerve cells in the central nervous system, the area damaged in spinal cord injury. It’s hoped the treatment will restore connections at the injury site, allowing patients to regain some movement and feeling.

Taking a closer look

Early results suggest the therapy is doing just that, and now follow-up studies, using MRIs, are adding weight to those findings.

The MRIs – taken six months after treatment – show that the five patients given a dose of 10 million AST-OPC1 cells had no evidence of lesion cavities in their spines. That’s important because often, after a spinal cord injury, the injury site expands and forms a cavity, caused by the death of nerve and support cells in the spine, that results in permanent loss of movement and function below the site, and additional neurological damage to the patient.

Another group of patients, treated in an earlier phase of the clinical trial, showed no signs of lesion cavities 12 months after their treatment.

Positively encouraging

In a news release, Dr. Edward Wirth, the Chief Medical Officer at Asterias, says this is very positive:

“These new follow-up results based on MRI scans are very encouraging, and strongly suggest that AST-OPC1 cells have engrafted in these patients post-implantation and have the potential to prevent lesion cavity formation, possibly reducing long-term spinal cord tissue deterioration after spinal cord injury.”

Because the safety data is also encouraging Asterias is now doubling the dose of cells that will be transplanted into patients to 20 million, in a separate arm of the trial. They are hopeful this dose will be even more effective in helping restore movement and function in patients.

We can’t wait to see what they find.

Stem cell stories that caught our eye: update on Capricor’s heart attack trial; lithium on the brain; and how stem cells do math

Capricor ALLSTARToday our partners Capricor Therapeutics announced that its stem cell therapy for patients who have experienced a large heart attack is unlikely to meet one of its key goals, namely reducing the scar size in the heart 12 months after treatment.

The news came after analyzing results from patients at the halfway point of the trial, six months after their treatment in the Phase 2 ALLSTAR clinical trial which CIRM was funding. They found that there was no significant difference in the reduction in scarring on the heart for patients treated with donor heart-derived stem cells, compared to patients given a placebo.

Obviously this is disappointing news for everyone involved, but we know that not all clinical trials are going to be successful. CIRM supported this research because it clearly addressed an unmet medical need and because an earlier Phase 1 study had showed promise in helping prevent decline in heart function after a heart attack.

Yet even with this failure to repeat that promise in this trial,  we learned valuable lessons.

In a news release, Dr. Tim Henry, Director of the Division of Interventional Technologies in the Heart Institute at Cedars-Sinai Medical Center and a Co-Principal Investigator on the trial said:

“We are encouraged to see reductions in left ventricular volume measures in the CAP-1002 treated patients, an important indicator of reverse remodeling of the heart. These findings support the biological activity of CAP-1002.”

Capricor still has a clinical trial using CAP-1002 to treat boys and young men developing heart failure due to Duchenne Muscular Dystrophy (DMD).

Lithium gives up its mood stabilizing secrets

As far back as the late 1800s, doctors have recognized that lithium can help people with mood disorders. For decades, this inexpensive drug has been an effective first line of treatment for bipolar disorder, a condition that causes extreme mood swings. And yet, scientists have never had a good handle on how it works. That is, until this week.

evan snyder

Evan Snyder

Reporting in the Proceedings of the National Academy of Sciences (PNAS), a research team at Sanford Burnham Prebys Medical Discovery Institute have identified the molecular basis of the lithium’s benefit to bipolar patients.  Team lead Dr. Evan Snyder explained in a press release why his group’s discovery is so important for patients:

“Lithium has been used to treat bipolar disorder for generations, but up until now our lack of knowledge about why the therapy does or does not work for a particular patient led to unnecessary dosing and delayed finding an effective treatment. Further, its side effects are intolerable for many patients, limiting its use and creating an urgent need for more targeted drugs with minimal risks.”

The study, funded in part by CIRM, attempted to understand lithium’s beneficial effects by comparing cells from patient who respond to those who don’t (only about a third of patients are responders). Induced pluripotent stem cells (iPSCs) were generated from both groups of patients and then the cells were specialized into nerve cells that play a role in bipolar disorder. The team took an unbiased approach by looking for differences in proteins between the two sets of cells.

The team zeroed in on a protein called CRMP2 that was much less functional in the cells from the lithium-responsive patients. When lithium was added to these cells the disruption in CRMP2’s activity was fixed. Now that the team has identified the molecular location of lithium’s effects, they can now search for new drugs that do the same thing more effectively and with fewer side effects.

The stem cell: a biological calculator?

math

Can stem cells do math?

Stem cells are pretty amazing critters but can they do math? The answer appears to be yes according to a fascinating study published this week in PNAS Proceedings of the National Academy of Sciences.

Stem cells, like all cells, process information from the outside through different receptors that stick out from the cells’ outer membranes like a satellite TV dish. Protein growth factors bind those receptors which trigger a domino effect of protein activity inside the cell, called cell signaling, that transfers the initial receptor signal from one protein to another. Ultimately that cascade leads to the accumulation of specific proteins in the nucleus where they either turn on or off specific genes.

Intuition would tell you that the amount of gene activity in response to the cell signaling should correspond to the amount of protein that gets into the nucleus. And that’s been the prevailing view of scientists. But the current study by a Caltech research team debunks this idea. Using real-time video microscopy filming, the team captured cell signaling in individual cells; in this case they used an immature muscle cell called a myoblast.

goentoro20170508

Behavior of cells over time after they have received a Tgf-beta signal. The brightness of the nuclei (circled in red) indicates how much Smad protein is present. This brightness varies from cell to cell, but the ratio of brightness after the signal to before the signal is about the same. Image: Goentoro lab, CalTech.

To their surprise the same amount of growth factor given to different myoblasts cells led to the accumulation of very different amounts of a protein called Smad3 in the cells’ nuclei, as much as a 40-fold difference across the cells. But after some number crunching, they discovered that dividing the amount of Smad3 after growth factor stimulation by the Smad3 amount before growth stimulation was similar in all the cells.

As team lead Dr. Lea Goentoro mentions in a press release, this result has some very important implications for studying human disease:

“Prior to this work, researchers trying to characterize the properties of a tumor might take a slice from it and measure the total amount of Smad in cells. Our results show that to understand these cells one must instead measure the change in Smad over time.”

Engineered bone tissue improves stem cell transplants

Bone marrow transplants are currently the only approved stem cell-based therapy in the United States. They involve replacing the hematopoietic, or blood-forming stem cells, found in the bone marrow with healthy stem cells to treat patients with cancers, immune diseases and blood disorders.

For bone marrow transplants to succeed, patients must undergo radiation therapy to wipe out their diseased bone marrow, which creates space for the donor stem cells to repopulate the blood system. Radiation can lead to complications including hair loss, nausea, fatigue and infertility.

Scientists at UC San Diego have a potential solution that could make current bone marrow transplants safer for patients. Their research, which was funded in part by a CIRM grant, was published yesterday in the journal PNAS.

Engineered bone with functional bone marrow in the center. (Varghese Lab)

Led by bioengineering professor Dr. Shyni Varghese, the team engineered artificial bone tissue that contains healthy donor blood stem cells. They implanted the engineered bone under the skin of normal mice and watched as the “accessory bone marrow” functioned like the real thing by creating new blood cells.

The implant lasted more than six months. During that time, the scientists observed that the cells within the engineered bone structure matured into bone tissue that housed the donor bone marrow stem cells and resembled how bones are structured in the human body. The artificial bones also formed connections with the mouse circulatory system, which allowed the host blood cells to populate the implanted bone tissue and the donor blood cells to expand into the host’s bloodstream.

Normal bone structure (left) and engineered bone (middle) are very similar. Bone tissue shown on top right and bone marrow cells on bottom right. (Varghese lab)

The team also implanted these artificial bones into mice that received radiation to mimic the procedures that patients typically undergo before bone marrow transplants. The engineered bone successfully repopulated the blood systems of the irradiated mice, similar to how blood stem cell functions in normal bone.

In a UC San Diego news release, Dr. Varghese explained how their technology could be translated into the clinic,

“We’ve made an accessory bone that can separately accommodate donor cells. This way, we can keep the host cells and bypass irradiation. We’re working on making this a platform to generate more bone marrow stem cells. That would have useful applications for cell transplantations in the clinic.”

The authors concluded that engineered bone tissue would specifically benefit patients who needed bone marrow transplants for non-cancerous bone marrow-related diseases such as sickle cell anemia or thalassemia where there isn’t a need to destroy cancer-causing cells.

A call to put the ‘public’ back in publication, and make stem cell research findings available to everyone

Opening the door

Opening the door to scientific knowledge

Thomas Gray probably wasn’t thinking about stem cell research when, in 1750 in his poem “Elegy in a Country Churchyard”, he wrote: “Full many a flower is born to blush unseen”. But a new study says that’s precisely what seems to happen to the findings of many stem cell clinical trials. They take place, but no details of their findings are ever made public. They blush, if they blush at all, unseen.

The study, in the journal Stem Cell Reports, says that only around 45 percent of stem cell clinical trials ever have their results published in peer-reviewed journals. Which means the results of around 55 percent of stem cell clinical trials are never shared with either the public or the scientific community.

Now, this finding apparently is not confined to stem cell research. Previous studies have shown a similar lack of publication of the results of more conventional therapies. Nonetheless, it’s a little disappointing – to say the least – to find out that so much knowledge and potentially valuable data is being lost due to lack of publication.

Definitely not full disclosure

Researchers at the University of Alberta in Canada used the US National Institute of Health’s (NIH) clinicaltrials.gov website as their starting point. They identified 1,052 stem cell clinical trials on the site. Only 393 trials were completed and of these, just 179 (45.4 percent) published their findings in a peer-reviewed journal.

In an interview in The Scientist, Tania Bubela, the lead researcher, says they chose to focus on stem cell clinical trials because of extensive media interest and the high public expectations for the field:

“When you have a field that is accused of over promising in some areas, it is beholden of the researchers in that field to publish the results of their trials so that the public and policy makers can realistically estimate the potential benefits.”

Now, it could be argued that publishing in a peer-reviewed journal is a rather high bar, that many researchers may have submitted articles but were rejected. However, there are other avenues for researchers to publish their findings, such as posting results on the clinicaltrials.gov database. Only 37 teams (3.5 percent) did that.

Why do it?

In the same article in The Scientist, Leigh Turner, a bioethicist at the University of Minnesota, raises the obvious question:

“The study shows a gap between studies that have taken place and actual publication of the data, so a substantial number of trials testing cell-based interventions are not entering the public domain. The underlying question is, what is the ethical and scientific basis to exposing human research subjects to risk if there is not going to be any meaningful contribution to knowledge at the end of the process?”

In short, why do it if you are not going to let anyone know what you did and what you found?

It’s a particularly relevant question when you consider that much of this research was supported with taxpayer dollars from the NIH and other institutions. So, if the public is paying for this research, doesn’t the public have a right to know what was learned?

Right to know

At CIRM we certainly think so. We expect and encourage all the researchers we fund to publish their findings. There are numerous ways and places to do that. For example, we expect each grantee to post a lay summary of their progress which we publish on our website. Stanford’s Dr. Joseph Wu’s progress reports for his work on heart disease shows you what those look like.

We also require researchers conducting clinical trials that we are funding to submit and post their trial results on the clinicaltrials.gov website.

The International Society for Stem Cell Research (ISSCR), agrees and recently updated its Guidelines for Stem Cell Research and Clinical Translation calling on researchers to publish, as fully as possible, their clinical trial results.

That is true regardless of whether or not the clinical trial showed it was both safe and effective, or whether it showed it was unsafe and ineffective. We can learn as much from failure as we can from success. But to do that we need to know what the results are.

Publishing only positive findings skews the scientific literature, and public perception of this work. Ignoring the negative could mean that other scientists waste a lot of time and money trying to do something that has already demonstrated it won’t work.

Publication should be a requirement for all research, particularly publicly funded research. It’s time to put the word “public” back in publication.

 

 

Keeping intestinal stem cells in their prime

Gut stem cells (green) in the small intestine of a mouse.

The average length of the human gut is 25 feet long. That’s equivalent to four really tall people or five really short people lined up head to toe. Intestinal stem cells have the fun job of regenerating and replacing ALL the cells that line the gut. Therefore, it’s important for these stem cells to be able to self-renew, a process that replenishes the stem cell population. If this important biological process is disrupted, the intestine is at risk for diseases like inflammatory bowel disease and cancer.

This week, Stanford Medicine researchers published new findings about the biological processes responsible for regulating the regenerative capacity of intestinal stem cells. Their work, which was partially funded by CIRM, was published in the journal Nature.

Priming gut stem cells to self-renew

Scientists know that the self-renewal of intestinal stem cells is very important for a happy, functioning gut, but the nuances of what molecules and signaling pathways regulate this process have yet to be figured out. The Stanford team, led by senior author and Stanford Professor Dr. Calvin Kuo, studied two signaling pathways, Wnt and R-Spondin, that are involved in the self-renewal of intestinal stem cells in mice.

Dr. Calvin Kuo, Stanford Medicine.

“The cascade of events comprising the Wnt signaling pathway is crucial to stem cell self-renewal,” Dr. Kuo explained in an email exchange. “The Wnt pathway can be induced by either hormones classified as “Wnts” or “R-spondins”.  However, it is not known if Wnts or R-spondins cooperate to induce Wnt signaling, and if these Wnts and R-spondins have distinct functions or if they can mutually substitute for each other.   We explored how Wnts and R-spondins might cooperate to regulate intestinal stem cells – which are extremely active and regenerate the 25-foot lining of the human intestine every week.”

The team used different reagents to activate or block Wnt or R-spondin signaling and monitored the effects on intestinal stem cells. They found that both were important for the self-renewal of intestinal stem cells, but that they played different roles.

“Our work revealed that Wnts and R-spondins are not equivalent and that they have very distinct functions even though they both trigger the Wnt signaling cascade,” said Dr. Kuo. “Both Wnts and R-spondins are required to maintain intestinal stem cells.  However, Wnts perform more of a subservient “priming” function, where they prepare intestinal stem cells for the action of R-spondin, which is the active catalyst for inducing intestinal stem cells to divide.”

The authors believe that this multi-step regulation, involving priming and self-renewal factors could apply to stem cell systems in other organs and tissues in the body. Some of the researchers on this study including Dr. Kuo are pursuing this idea through a new company called Surrozen, which produces artificial bioengineered Wnt molecules that don’t require activation like natural Wnt molecules. These Wnt molecules were used in the current study and are explained in more detail in a separate Nature article published at the same time.

The company believes that artificial Wnts will be useful for understanding stem cell biology and potentially for therapeutic applications. Dr. Kuo explained,

“The new surrogate Wnts are easily produced and can circulate in the bloodstream, unlike natural Wnts.  There may be medical applications of these bioengineered Wnt surrogates in stimulating various stem cell compartments of the body, given the wide range of stem cells that are governed by natural Wnts.”

jCyte gets FDA go-ahead for Fast Track review process of Retinitis Pigmentosa stem cell therapy

21 century cures

When the US Congress approved, and President Obama signed into law, the 21st Century Cures Act last year there was guarded optimism that this would help create a more efficient and streamlined, but no less safe, approval process for the most promising stem cell therapies.

Even so many people took a wait and see approach, wanting a sign that the Food and Drug Administration (FDA) would follow the recommendations of the Act rather than just pay lip service to it.

This week we saw encouraging signs that the FDA is serious when it granted Regenerative Medicine Advanced Therapy (RMAT) status to the CIRM-funded jCyte clinical trial for a rare form of blindness. This is a big deal because RMAT seeks to accelerate approval for stem cell therapies that demonstrate they can help patients with unmet medical needs.

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jCyte co-founder Dr. Henry Klassen

jCyte’s work is targeting retinitis pigmentosa (RP), a genetic disease that slowly destroys the cells in the retina, the part of the eye that converts light into electrical signals which the brain then interprets as vision. At first people with RP lose their night and peripheral vision, then the cells that help us see faces and distinguish colors are damaged. RP usually strikes people in their teens and, by the time they are 40, many people are legally blind.

jCyte’s jCell therapy uses what are called retinal progenitor cells, injected into the eye, which then release protective factors to help repair and rescue diseased retinal cells. The hope is this will stop the disease’s progression and even restore some vision to people with RP.

Dr. Henry Klassen, jCyte’s co-founder and a professor at UC Irvine, was understandably delighted by the designation. In a news release, he said:

“This is uplifting news for patients with RP. At this point, there are no therapies that can help them avoid blindness. We look forward to working with the FDA to speed up the clinical development of jCell.”

FDA

On the FDA’s blog – yes they do have one – it says researchers:

“May obtain the RMAT designation for their drug product if the drug is intended to treat serious or life-threatening diseases or conditions and if there is preliminary clinical evidence indicating that the drug has the potential to address unmet medical needs for that disease or condition. Sponsors of RMAT-designated products are eligible for increased and earlier interactions with the FDA, similar to those interactions available to sponsors of breakthrough-designated therapies. In addition, they may be eligible for priority review and accelerated approval.”

Paul Bresge

jCyte CEO Paul Bresge

jCyte is one of the first to get this designation, a clear testimony to the quality of the work done by Dr. Klassen and his team. jCyte CEO Paul Bresge says it may help speed up their ability to get this treatment to patients.

 

“We are gratified by the FDA’s interest in the therapeutic potential of jCell and greatly appreciate their decision to provide extra support. We are seeing a lot of momentum with this therapy. Because it is well-tolerated and easy to administer, progress has been rapid. I feel a growing sense of excitement among patients and clinicians. We look forward to getting this critical therapy over the finish line as quickly as possible.”

Regular readers of this blog will already be familiar with the story of Rosie Barrero, one of the first group of people with RP who got the jCell therapy. Rosie says it has helped restore some vision to the point where she is now able to read notes she wrote ten years ago, distinguish colors and, best of all, see the faces of her children.

RMAT is no guarantee the therapy will be successful. But if the treatment continues to show promise, and is safe, it could mean faster access to a potentially life-changing therapy, one that could ultimately rescue many people from a lifetime of living in the dark.

 

 

CIRM’s Randy Mills leaving stem cell agency to take on new challenge

Mills, Randy Union Tribune K.C. Alfred

Some news releases are fun to write. Some less so. The one that CIRM posted today definitely falls into that latter group. It announced that CIRM’s President and CEO, Randy Mills, is leaving us to take up the role of President and CEO at the National Marrow Donor Program – NMPD/Be The Match.

It’s a great opportunity for him but a big loss for us.

Be The Match is a non-profit organization that delivers cures to patients in need of a life-saving marrow or cord blood transplant. The organization operates the national Be The Match Registry®—the world’s largest listing of potential marrow donors and donated umbilical cord blood units—matches patients with their marrow donor, educates healthcare professionals and conducts research so more lives can be saved. The organization also recently created a subsidiary—Be The Match BioTherapiesSM—that supports organizations pursuing new life-saving treatments in cellular therapy.

Randy has been at CIRM since April 2014. In that time he has dramatically re-shaped the agency, and, more importantly, dramatically improved the speed with which we are able to fund research. It’s no exaggeration to say that Randy’s drive to create CIRM 2.0 was a radical overhaul of the way we work. It made it easier for researchers to apply to us for funding, made our funding cycles more consistent and the application process simpler – though no less rigorous.

As our CIRM Board Chair Jonathan Thomas said in the news release:

“CIRM has experienced a remarkable transformation since Randy’s arrival. He has taken the agency to a new level by developing and implementing a bold strategic plan, the results of which include an 82% reduction in approval time for clinical trial projects, a 3-fold increase in the number of clinical trials, and a 65% reduction in the time it takes to enroll those trials. The opportunity for Randy to lead a tremendously important organization such as the NMDP/Be The Match is consistent with the values he demonstrated at CIRM, which put the well-being of patients above all else. We shall miss him but know he will do great things at NMDP/Be The Match.”

From a personal perspective, what most impressed me about Randy was his willingness to involve every person in the agency in changing the way we work. He could easily have come in and simply issued orders and told people what to do. Instead he invited every person at CIRM to sit in on the meetings that were shaping the new direction we took. You didn’t have to go, but if you did you were expected to offer thoughts and ideas. No sitting idly by.

Those meetings not only changed the direction of the agency, they also re-energized the agency. When people feel their voice is being heard, that their opinion has value, they respond by working harder and smarter.

The CIRM of today has the same mission as always – accelerating stem cell treatments to patients with unmet medical needs – but the people working here seem to have a renewed commitment to making that mission a reality.

Randy brought to CIRM energy and a renewed sense of purpose, along with some truly terrible jokes and a strange conviction that he could have been a great rock and roll drummer (suffice to say he made the right career choice when he went into research).

He changed us as an agency, for the better. We shall miss him, but know he will do great things in his new role at NMDP/Be The Match and we wish him success in his new job, and his family great joy in their new home.

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Maria Millan

Randy will be with us till the end of June and starting July 1st Dr. Maria Millan will take on the role of interim President and CEO.