Encouraging news for treatment targeting retinitis pigmentosa

While most people probably wouldn’t put 2020 in their list of favorite years, it’s certainly turning out to be a good one for jCyte. Earlier this year jCyte entered into a partnership with global ophthalmology company Santen Pharmaceuticals worth up to $252 million. Then earlier this week they announced some encouraging results from their Phase 2b clinical trial.

Let’s back up a bit and explain what jCyte does and why it’s so important. They have developed a therapy for retinitis pigmentosa (RP), a rare vision destroying disease that attacks the light sensitive cells at the back of the eye. People are often diagnosed when they are in their teens and most are legally blind by middle age. CIRM has supported this therapy from its early stages into clinical trials.

This latest clinical trial is one of the largest of its kind anywhere in the world. They enrolled 84 patients (although only 74 were included in the final analysis). The patients had vision measuring between 20/80 and 20/800. They were split into three groups: one group was given a sham or placebo treatment; one was given three million human retinal progenitor cells (hRPCs), the kind attacked by the disease; and one was given six million hRPCs.

jCyte CEO Paul Bresge

In an article in Endpoints News, jCyte’s CEO Paul Bresge said there was a very specific reason for this approach. “We did enroll a very wide patient population into our Phase IIb, including patients that had vision anywhere from 20/80 to 20/800, just to learn which patients would potentially be the best responders.”

The results showed that the treatment group experienced improved functional vision and greater clarity of vision compared to the sham or placebo group. Everyone had their vision measured at the start and again 12 months later. For the placebo group the mean change in their ability to read an eye chart (with glasses on) was an improvement of 2.81 letters; for the group that got three million hRPCs it was 2.96 letters, and for the group that got six million hRPCs it was 7.43 letters.

When they looked at a very specific subgroup of patients the improvement was even more dramatic, with the six million cell group experiencing an improvement of 16.27 letters.

Dr. Henry Klassen

Dr. Henry Klassen, one of the founders of jCyte, says the therapy works by preserving the remaining photoreceptors in the eye, and helping them bounce back.

“Typically, people think about the disease as a narrowing of this peripheral vision in a very nice granular way, but that’s actually not what happens. What happens in the disease is that patients lose like islands of vision. So, what we’re doing in our tests is actually measuring […] islands that the patients have at baseline, and then what we’re seeing after treatment is that the islands are expanding. It’s similar to the way that one would track, let’s say a tumor, in oncology of course we’re looking for the opposite effect. We’re looking for the islands of vision to expand.”

One patient did experience some serious side effects in the trial but they responded well to treatment.

The team now plan on carrying out a Phase 3 clinical trial starting next year. They hope that will provide enough evidence showing the treatment is both safe and effective to enable them to get approval from the US Food and Drug Administration to make it available to all who need it.

Lab-grown human sperm cells could unlock treatments for infertility

Dr. Miles Wilkinson: Photo courtesy UCSD

Out of 100 couples in the US, around 12 or 13 will have trouble starting a family. In one third of those cases the problem is male infertility (one third is female infertility and the other third is a combination of factors). In the past treatment options for men were often limited. Now a new study out of the University of California San Diego (UCSD) could help lead to treatments to help these previously infertile men have children of their own.

The study, led by Dr. Miles Wilkinson of UCSD School of Medicine, targeted spermatogonial stem cells (SSCs), which are the cells that develop into sperm. In the past it was hard to isolate these SSCs from other cells in the testes. However, using a process called single cell RNA sequencing – which is like taking a photo of all the gene expression happening in one cell at a precise moment – the team were able to identify the SSCs.

In a news release Dr. Wilkinson, the senior author of the study, says this is a big advance on previous methods: “We think our approach — which is backed up by several techniques, including single-cell RNA-sequencing analysis — is a significant step toward bringing SSC therapy into the clinic.”

Identifying the SSCs was just the first step. Next the team wanted to find a way to be able to take those cells and grow and multiply them in the lab, an important step in having enough cells to be able to treat infertility.

So, they tested the cells in the lab and identified something called the AKT pathway, which controls cell division and survival. By blocking the AKT pathway they were able to keep the SSCs alive and growing for a month. Next they hope to build on the knowledge and expand the cells for even longer so they could be used in a clinical setting.

This image has an empty alt attribute; its file name is wilkinson-ssc-graphic_450px.jpg
Illustrations by Vishaala Wilkinson

The hope is that this could ultimately lead to treatments for men whose bodies don’t produce sperm cells, or enough sperms cells to make them fertile. It could also help children going through cancer therapy which can destroy their ability to have children of their own later in life. By taking sperm cells and freezing them, they could later be grown and expanded in the lab and injected back into the testes to restore sperm production.

The study is published in the journal Proceedings of the National Academy of Science.

A ready-made approach to tackling COVID-19

Coronavirus particles, illustration.

In late March the CIRM Board approved $5 million in emergency funding for COVID-19 research. The idea was to support great ideas from California’s researchers, some of which had already been tested for different conditions, and see if they could help in finding treatments or a vaccine for the coronavirus.

Less than a month later we were funding a clinical trial and two other projects, one that targeted a special kind of immune system cell that has the potential to fight the virus.

Our friends at UCLA have just written a terrific piece on this project and the team that came up with the idea. Here is that article.

Researchers use stem cells to model the immune response to COVID-19

By Tiare Dunlap

Cities across the United States are opening back up, but we’re still a long way from making the COVID-19 pandemic history. To truly accomplish that, we need to have a vaccine that can stop the spread of infection.

But to develop an effective vaccine, we need to understand how the immune system responds to SARS-CoV-2, the virus that causes COVID-19.

Vaccines work by imitating infection. They expose a person’s immune system to a weakened version or component of the virus they are intended to protect against. This essentially prepares the immune system to fight the virus ahead of time, so that if a person is exposed to the real virus, their immune system can quickly recognize the enemy and fight the infection. Vaccines need to contain the right parts of the virus to provoke a strong immune response and create long-term protection.

Most of the vaccines in development for SARS CoV-2 are using part of the virus to provoke the immune system to produce proteins called antibodies that neutralize the virus. Another way a vaccine could create protection against the virus is by activating the T cells of the immune system.

T cells specifically “recognize” virus-infected cells, and these kinds of responses may be especially important for providing long-term protection against the virus. One challenge for researchers is that they have only had a few months to study how the immune system protects against SARS CoV-2, and in particular, which parts of the virus provoke the best T-cell responses.

This is where immunotherapy researchers and UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research members Dr. Gay Crooks and Dr. Christopher Seet come in.

Dr. Gay Crooks: Photo courtesy UCLA

For years, they have been perfecting an innovative technology that uses blood-forming stem cells — which can give rise to all types of blood and immune cells — to produce a rare and powerful subset of immune cells called type 1 dendritic cells. Type 1 dendritic cells play an essential role in the immune response by devouring foreign proteins, termed antigens, from virus-infected cells and then chopping them into fragments. Dendritic cells then use these protein fragments to trigger T cells to mount an immune response.

Dr. Christopher Seet: Photo courtesy UCLA

Using this technology, Crooks and Seet are working to pinpoint which specific parts of the SARS-CoV-2 virus provoke the strongest T-cell responses.

Building long-lasting immunity

“We know from a lot of research into other viral infections and also in cancer immunotherapy, that T-cell responses are really important for long-lasting immunity,” said Seet, an assistant professor of hematology-oncology at the David Geffen School of Medicine at UCLA. “And so this approach will allow us to better characterize the T-cell response to SARS-CoV-2 and focus vaccine and therapeutic development on those parts of the virus that induce strong T-cell immunity.”

This project was recently awarded $150,000 from the California Institute for Regenerative Medicine, the state’s stem cell agency. The award was matched by the UCLA Broad Stem Cell Research Center.

Crooks’ and Seet’s project uses blood-forming stem cells taken from healthy donors and infected with a virus containing antigens from SARS-CoV-2. They then direct these stem cells to produce large numbers of type 1 dendritic cells using a new method developed by Seet and Suwen Li, a graduate student in Crooks’ lab. Both Seet and Li are graduates of the UCLA Broad Stem Cell Research Center’s training program.

“The dendritic cells we are able to make using this process are really good at chopping up viral antigens and eliciting strong immune responses from T cells,” said Crooks, a professor of pathology and laboratory medicine and of pediatrics at the medical school and co-director of the UCLA Broad Stem Cell Research Center.

When type 1 dendritic cells chop up viral antigens into fragments, they present these fragments on their cell surfaces to T cells. Our bodies produce millions and millions of T cells each day, each with its own unique antigen receptor, however only a few will have a receptor capable of recognizing a specific antigen from a virus.

When a T cell with the right receptor recognizes a viral antigen on a dendritic cell as foreign and dangerous, it sets off a chain of events that activates multiple parts of the immune system to attack cells infected with the virus. This includes clonal expansion, the process by which each responding T cell produces a large number of identical cells, called clones, which are all capable of recognizing the antigen.

“Most of those T cells will go off and fight the infection by killing cells infected with the virus,” said Seet, who, like Crooks, is also a member of the UCLA Jonsson Comprehensive Cancer Center. “However, a small subset of those cells become memory T cells — long-lived T cells that remain in the body for years and protect from future infection by rapidly generating a robust T-cell response if the virus returns. It’s immune memory.”

Producing extremely rare immune cells

This process has historically been particularly challenging to model in the lab, because type 1 dendritic cells are extremely rare — they make up less than 0.1% of cells found in the blood. Now, with this new stem cell technology, Crooks and Seet can produce large numbers of these dendritic cells from blood stem cells donated by healthy people, introduce them to parts of the virus, then see how T cells  taken from the blood can respond in the lab. This process can be repeated over and over using cells taken from a wide range of healthy people.

“The benefit is we can do this very quickly without the need for an actual vaccine trial, so we can very rapidly figure out in the lab which parts of the virus induce the best T-cell responses across many individuals,” Seet said.

The resulting data could be used to inform the development of new vaccines for COVID-19 that improve T-cell responses. And the data about which viral antigens are most important to the T cells could also be used to monitor the effectiveness of existing vaccine candidates, and an individual’s immune status to the virus.

“There are dozens of vaccine candidates in development right now, with three or four of them already in clinical trials,” Seet said. “We all hope one or more will be effective at producing immediate and long-lasting immunity. But as there is so much we don’t know about this new virus, we’re still going to need to really dig in to understand how our immune systems can best protect us from infection.”

Supporting basic research into our body’s own processes that can inform new strategies to fight disease is central to the mission of the Broad Stem Cell Research Center.

“When we started developing this project some years ago, we had no idea it would be so useful for studying a viral infection, any viral infection,” Crooks said. “And it was only because we already had these tools in place that we could spring into action so fast.”

Parkinson’s Disease and Stem Cells

Lila Collins, PhD

A few weeks ago we held a Facebook Live “Ask the Stem Cell Team About Parkinson’s Disease” event. As you can imagine we got lots of questions but, because of time constraints, only had time to answer a few. Thanks to my fabulous CIRM colleagues, Dr. Lila Collins and Dr. Kent Fitzgerald, for putting together answers to some of the other questions. Here they are.

Kent Fitzgerald, PhD

Q: It seems like we have been hearing for years that stem cells can help people with Parkinson’s, why is it taking so long?

A: Early experiments in Sweden using fetal tissue did provide a proof of concept for the strategy of replacing dopamine producing cells damaged or lost in Parkinson’s disease (PD) . At first, this seemed like we were on the cusp of a cell therapy cure for PD, however, we soon learned based on some side effects seen with this approach (in particular dyskinesias or uncontrollable muscle movements) that the solution was not as simple as once thought. 

While this didn’t produce the answer it did provide some valuable lessons.

The importance of dopaminergic (DA) producing cell type and the location in the brain of the transplant.  Simply placing the replacement cells in the brain is not enough. It was initially thought that the best site to place these DA cells is a region in the brain called the SN, because this area helps to regulate movement. However, this area also plays a role in learning, emotion and the brains reward system. This is effectively a complex wiring system that exists in a balance, “rewiring” it wrong can have unintended and significant side effects. 

Another factor impacting progress has been understanding the importance of disease stage. If the disease is too advanced when cells are given then the transplant may no longer be able to provide benefit.  This is because DA transplants replace the lost neurons we use to control movement, but other connected brain systems have atrophied in response to losing input from the lost neurons. There is a massive amount of work (involving large groups and including foundations like the Michael J Fox Foundation) seeking to identify PD early in the disease course where therapies have the best chance of showing an effect.   Clinical trials will ultimately help to determine the best timing for treatment intervention.

Ideally, in addition to the cell therapies that would replace lost or damaged cells we also want to find a therapy that slows or stops the underlying biology causing progression of the disease.

So, I think we’re going to see more gene therapy trials including those targeting the small minority of PD that is driven by known mutations.  In fact, Prevail Therapeutics will soon start a trial in patients with GBA1 mutations. Hopefully, replacing the enzyme in this type of genetic PD will prevent degeneration.

And, we are also seeing gene therapy approaches to address forms of PD that we don’t know the cause, including a trial to rescue sick neurons with GDNF which is a neurotrophic factor (which helps support the growth and survival of these brain cells) led by Dr Bankiewicz  and trials by Axovant and Voyager, partnered with Neurocrine aimed at restoring dopamine generation in the brain.

 A small news report came out earlier this year about a recently completed clinical trial by Roche Pharma and Prothena. This addressed the build up in the brain of what are called lewy bodies, a problem common to many forms of PD. While the official trial results aren’t published yet, a recent press release suggests reason for optimism.  Apparently, the treatment failed to statistically improve the main clinical measurement, but other measured endpoints saw improvement and it’s possible an updated form of this treatment will be tested again in the hopes of seeing an improved effect.

Finally, I’d like to call attention to the G force trials. Gforce is a global collaborative effort to drive the field forward combining lessons learned from previous studies with best practices for cell replacement in PD.  These first-in-human safety trials to replace the dopaminergic neurons (DANs) damaged by PD have shared design features including identifying what the best goals are and how to measure those.

The CIRA trial, Dr Jun Takahashi

The NYSTEM PD trial, Dr Lorenz Studer

The EUROSTEMPD trial, Dr Roger Barker.

And the Summit PD trial, Dr Jeanne Loring of Aspen Neuroscience.

Taken together these should tell us quite a lot about the best way to replace these critical neurons in PD.

As with any completely novel approach in medicine, much validation and safety work must be completed before becoming available to patients

The current approach (for cell replacement) has evolved significantly from those early studies to use cells engineered in the lab to be much more specialized and representing the types believed to have the best therapeutic effects with low probability of the side effects (dyskinesias) seen in earlier trials. 

If we don’t really know the cause of Parkinson’s disease, how can we cure it or develop treatments to slow it down?

PD can now be divided into major categories including 1. Sporadic, 2. Familial. 

For the sporadic cases, there are some hallmarks in the biology of the neurons affected in the disease that are common among patients.  These can be things like oxidative stress (which damages cells), or clumps of proteins (like a-synuclein) that serve to block normal cell function and become toxic, killing the DA neurons. 

The second class of “familial” cases all share one or more genetic changes that are believed to cause the disease.  Mutations in genes (like GBA, LRRK2, PRKN, SNCA) make up around fifteen percent of the population affected, but the similarity in these gene mutations make them attractive targets for drug development.

CIRM has funded projects to generate “disease in a dish” models using neurons made from adults with Parkinson’s disease.   Stem cell-derived models like this have enabled not only a deep probing of the underlying biology in Parkinson’s, which has helped to identify new targets for investigation, but have also allowed for the testing of possible therapies in these cell-based systems. 

iPSC-derived neurons are believed to be an excellent model for this type of work as they can possess known familial mutations but also show the rest of the patients genetic background which may also be a contributing factor to the development of PD. They therefore contain both known and unknown factors that can be tested for effective therapy development.

I have heard of scientists creating things called brain organoids, clumps of brain cells that can act a little bit like a brain. Can we use these to figure out what’s happening in the brain of people with Parkinson’s and to develop treatments?

There is considerable excitement about the use of brain organoids as a way of creating a model for the complex cell-to-cell interactions in the brain.  Using these 3D organoid models may allow us to gain a better understanding of what happens inside the brain, and develop ways to treat issues like PD.

The organoids can contain multiple cell types including microglia which have been a hot topic of research in PD as they are responsible for cleaning up and maintaining the health of cells in the brain.  CIRM has funded the Salk Institute’s Dr. Fred Gage’s to do work in this area.

If you go online you can find lots of stem cells clinics, all over the US, that claim they can use stem cells to help people with Parkinson’s. Should I go to them?

In a word, no! These clinics offer a wide variety of therapies using different kinds of cells or tissues (including the patient’s own blood or fat cells) but they have one thing in common; none of these therapies have been tested in a clinical trial to show they are even safe, let alone effective. These clinics also charge thousands, sometimes tens of thousands of dollars these therapies, and because it’s not covered by insurance this all comes out of the patient’s pocket.

These predatory clinics are peddling hope, but are unable to back it up with any proof it will work. They frequently have slick, well-designed websites, and “testimonials” from satisfied customers. But if they really had a treatment for Parkinson’s they wouldn’t be running clinics out of shopping malls they’d be operating huge medical centers because the worldwide need for an effective therapy is so great.

Here’s a link to the page on our website that can help you decide if a clinical trial or “therapy” is right for you.

Is it better to use your own cells turned into brain cells, or cells from a healthy donor?

This is the BIG question that nobody has evidence to provide an answer to. At least not yet.

Let’s start with the basics. Why would you want to use your own cells? The main answer is the immune system.  Transplanted cells can really be viewed as similar to an organ (kidney, liver etc) transplant. As you likely know, when a patient receives an organ transplant the patient’s immune system will often recognize the tissue/organ as foreign and attack it. This can result in the body rejecting what is supposed to be a life-saving organ. This is why people receiving organ transplants are typically placed on immunosuppressive “anti-rejection “drugs to help stop this reaction. 

In the case of transplanted dopamine producing neurons from a donor other than the patient, it’s likely that the immune system would eliminate these cells after a short while and this would stop any therapeutic benefit from the cells.  A caveat to this is that the brain is a “somewhat” immune privileged organ which means that normal immune surveillance and rejection doesn’t always work the same way with the brain.  In fact analysis of the brains collected from the first Swedish patients to receive fetal transplants showed (among other things) that several patients still had viable transplanted cells (persistence) in their brains.

Transplanting DA neurons made from the patient themselves (the iPSC method) would effectively remove this risk of the immune system attack as the cells would not be recognized as foreign.

CIRM previously funded a discovery project with Jeanne Loring from Scripps Research Institute that sought to generate DA neurons from Parkinson’s patients for use as a potential transplant therapy in these same patients.   This project has since been taken on by a company formed, by Dr Loring, called Aspen Neuroscience.  They hope to bring this potential therapy into clinical trials in the near future.    

A commonly cited potential downside to this approach is that patients with genetic (familial) Parkinson’s would be receiving neurons generated with cells that may have the same mutations that caused the problem in the first place. However, as it can typically take decades to develop PD, these cells could likely function for a long time. and prove to be better than any current therapies.

Creating cells from each individual patient (called autologous) is likely to be very expensive and possibly even cost-prohibitive. That is why many researchers are working on developing an “off the shelf” therapy, one that uses cells from a donor (called allogeneic)would be available as and when it’s needed.

When the coronavirus happened, it seemed as if overnight the FDA was approving clinical trials for treatments for the virus. Why can’t it work that fast for Parkinson’s disease?

While we don’t know what will ultimately work for COVID-19, we know what the enemy looks like.  We also have lots of experience treating viral infections and creating vaccines.  The coronavirus has already been sequenced, so we are building upon our understanding of other viruses to select a course to interrupt it.  In contrast, the field is still trying to understand the drivers of PD that would respond to therapeutic targeting and therefore, it’s not precisely clear how best to modify the course of neurodegenerative disease.  So, in one sense, while it’s not as fast as we’d like it to be, the work on COVID-19 has a bit of a head start.

Much of the early work on COVID-19 therapies is also centered on re-purposing therapies that were previously in development.  As a result, these potential treatments have a much easier time entering clinical trials as there is a lot known about them (such as how safe they are etc.).  That said, there are many additional therapeutic strategies (some of which CIRM is funding) which are still far off from being tested in the clinic. 

The concern of the Food and Drug Administration (FDA) is often centered on the safety of a proposed therapy.  The less known, the more cautious they tend to be. 

As you can imagine, transplanting cells into the brain of a PD patient creates a significant potential for problems and so the FDA needs to be cautious when approving clinical trials to ensure patient safety.

CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

Promising results from CIRM-funded projects

Severe Leukocyte Adhesion Deficiency-1 (LAD-1) is a rare condition that causes the immune system to malfunction and reduces its ability to fight off viruses and bacteria. Over time the repeated infections can take a heavy toll on the body and dramatically shorten a person’s life. But now a therapy, developed by Rocket Pharmaceuticals, is showing promise in helping people with this disorder.

The therapy, called RP-L201, targets white blood cells called neutrophils which ordinarily attack and destroy invading particles. In people with LAD-1 their neutrophils are dangerously low. That’s why the new data about this treatment is so encouraging.

In a news release, Jonathan Schwartz, M.D., Chief Medical Officer of Rocket, says early results in the CIRM-funded clinical trial, show great promise:

“Patients with severe LAD-I have neutrophil CD18 expression of less than 2% of normal, with extremely high mortality in early childhood. In this first patient, an increase to 47% CD18 expression sustained over six months demonstrates that RP-L201 has the potential to correct the neutrophil deficiency that is the hallmark of LAD-I. We are also pleased with the continued visible improvement of multiple disease-related skin lesions. The second patient has recently been treated, and we look forward to completing the Phase 1 portion of the registrational trial for this program.”

The results were released at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy.

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These microscopic images show gene expression in muscle stem and progenitor cells as they mature from early development to adulthood (left to right). As part of this process, the cells switch from actively expressing one key gene (green) to another (violet); this is accompanied by the growth of muscle fibers (red).
Photo courtesy: Cell Stem Cell/UCLA Broad Stem Cell Research Center

When you are going on a road-trip you need a map to help you find your way. It’s the same with stem cell research. If you are going to develop a new way to treat devastating muscle diseases, you need to have a map to show you how to build new muscle stem cells. And that’s what researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA – with help from CIRM funding – have done.

The team took muscle progenitor cells – which show what’s happening in development before a baby is born – and compared them to muscle stem cells – which control muscle development after a baby is born. That enabled them to identify which genes are active at what stage of development.

In a news release, April Pyle, senior author of the paper, says this could open the door to new therapies for a variety of conditions:

“Muscle loss due to aging or disease is often the result of dysfunctional muscle stem cells. This map identifies the precise gene networks present in muscle progenitor and stem cells across development, which is essential to developing methods to generate these cells in a dish to treat muscle disorders.”

The study is published in the journal Cell Stem Cell.

A clear vision for the future

Dr. Henry Klassen and Dr. Jing Yang, founders of jCyte

When you have worked with a group of people over many years the relationship becomes more than just a business venture, it becomes personal. That’s certainly the case with jCyte, a company founded by Drs. Henry Klassen and Jing Yang, aimed at finding a cure for a rare form of vision loss called retinitis pigmentosa. CIRM has been supporting this work since it’s early days and so on Friday, the news that jCyte has entered into a partnership with global ophthalmology company Santen was definitely a cause for celebration.

The partnership could be worth up to $252 million and includes an immediate payment of $62 million. The agreement also connects jCyte to Santen’s global business and medical network, something that could prove invaluable in bringing their jCell therapy to patients outside the US.

Here in the US, jCyte is getting ready to start a Phase 2 clinical trial – which CIRM is funding – that could prove pivotal in helping it get approval from the US Food and Drug Administration.

As Dr. Maria Millan, CIRM’s President and CEO says, we have been fortunate to watch this company steadily progress from having a promising idea to developing a life-changing therapy.

“This is exciting news for everyone at jCyte. They have worked so hard over many years to develop their therapy and this partnership is a reflection of just how much they have achieved. For us at CIRM it’s particularly encouraging. We have supported this work from its early stages through clinical trials. The people who have benefited from the therapy, people like Rosie Barrero, are not just patients to us, they have become friends. The people who run the company, Dr. Henry Klassen, Dr. Jing Yang and CEO Paul Bresge, are so committed and so passionate about their work that they have overcome many obstacles to bring them here, an RMAT designation from the Food and Drug Administration, and a deal that will help them advance their work even further and faster. That is what CIRM is about, following the science and the mission.”

Paul Bresge, jCyte’s CEO says they couldn’t have done it without CIRM’s early and continued investment.

Paul Bresge, jCyte CEO

“jCyte is extremely grateful to CIRM, which was established to support innovative regenerative medicine programs and research such as ours.  CIRM supported our early preclinical data all the way through our late stage clinical trials.  This critical funding gave us the unique ability and flexibility to put patients first in each and every decision that we made along the way. In addition to the funding, the guidance that we have received from the CIRM team has been invaluable. jCell would not be possible without the early support from CIRM, our team at jCyte, and patients with degenerative retinal diseases are extremely appreciative for your support.”

Here is Rosie Barrero talking about the impact jCell has had on her life and the life of her family.

A true Hall of Fame winner

Dr. Larry Goldstein: Photo courtesy UCSD

You know you are working with some of the finest scientific minds in the world when they get elected to the prestigious National Academy of Sciences (NAS). It’s the science equivalent of the baseball, football or even Rock and Roll Hall of Fame. People only get in if their peers vote them in. It’s considered one of the highest honors in science, one earned over many decades of hard work. And when it comes to hard work there are few people who work harder than U.C. San Diego’s Dr. Lawrence Goldstein, one of the newly elected members of the NAS.

Dr. Goldstein – everyone calls him Larry – was the founder and director of the UCSD Stem Cell Program and the Sanford Stem Cell Clinical Center at UC San Diego Health and is founding scientific director of the Sanford Consortium for Regenerative Medicine.

For more than 25 years Larry’s work has targeted the brain and, in particular, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) better known as Lou Gehrig’s disease.

In 2012 his team was the first to create stem cell models for two different forms of Alzheimer’s, the hereditary and the sporadic forms. This gave researchers a new way of studying the disease, helping them better understand what causes it and looking at new ways of treating it.

His work has also helped develop a deeper understanding of the genetics of Alzheimer’s and to identify possible new targets for stem cell and other therapies.

Larry was typically modest when he heard the news, saying: “I have been very fortunate to have wonderful graduate students and fellows who have accomplished a great deal of excellent research. It is a great honor for me and for all of my past students and fellows – I am obviously delighted and hope to contribute to the important work of the National Academy of Sciences.”

But Larry doesn’t intend to rest on his laurels. He says he still has a lot of work to do, including “raising funding to test a new drug approach for Alzheimer’s disease that we’ve developed with CIRM support.”

Jennifer Briggs Braswell, PhD, worked with Larry at UCSD from 2005 to 2018. She says Larry’s election to the NAS is well deserved:

“His high quality publications, the pertinence of his studies in neurodegeneration to our current problems, and his constant, unwavering devotion to the next generation of scientists is matched only by his dedication to improving public understanding of science to motivate social, political, and financial support.  

“He has been for me a supportive mentor, expressing enthusiastic belief in the likely success of my good ideas and delivering critique with kindness and sympathy.   He continues to inspire me, our colleagues at UCSD and other communities, advocate publicly for the importance of science, and work tirelessly on solutions for neurodegenerative disorders.”

You can read about Larry’s CIRM-supported work here.

You can watch an interview with did with Larry a few years ago.

Huge honor, hugely deserved for CIRM-funded stem cell researcher

Dr. Andy McMahon: Photo courtesy USC

Andy McMahon is one of the most understated, humble and low-key people you are ever likely to meet. He’s also one of the smartest. And he has a collection of titles to prove it. He is the W.M. Keck Provost and University Professor in USC’s departments of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine, and Biological Sciences at the Dornsife College of Letters, Arts and Sciences, a fellow of the American Association for the Advancement of Science, the American Academy of Arts and Sciences, the European Molecular Biology Organization, and the Royal Society.

Now you can add to that list that Andy is a member of the National Academy of Sciences (NAS). Election to the NAS is no ordinary honor. It’s one of the highest in the scientific world.

In a USC news release Dean Laura Mosqueda from the Keck School praised Andy saying: “We’re delighted that Dr. McMahon is being recognized as a newly elected member of the National Academy of Sciences. Because new members are elected by current members, this represents recognition of Dr. McMahon’s achievements by his most esteemed peers in all scientific fields.”

Not surprisingly CIRM has funded some of Andy’s work – well, we do pride ourselves on working with the best and brightest scientists – and that research is taking on added importance with the spread of COVID-19. Andy’s area of specialty is kidneys, trying to develop new ways to repair damaged or injured kidneys. Recent studies show that between 3 and 9 percent of patients with COVID-19 develop an acute kidney injury; in effect their kidneys suddenly stop working and many of these patients have to undergo dialysis to stay alive.

Even those who recover are at increased risk for developing more chronic, even end-stage kidney disease. That’s where Andy’s work could prove most useful. His team are using human stem cells to create mini artificial kidneys that have many of the same properties as the real thing. These so-called “organoids” enable us to study chronic kidney disease, come up with ideas to repair damage or slow down the progression of the disease, even help improve the chances of a successful transplant if that becomes necessary.

You can hear Andy talk about his work here:

CIRM is now funding a number of projects targeting COVID-19, including a clinical trial using convalescent plasma gel, and intends investing in more in the coming weeks and months. You can read about that here.

We are also funding several clinical trials targeting kidney failure. You can read about those on our Clinical Trials Dashboard page – diseases are listed alphabetically.

Stem Cells for Parkinson’s Disease

While the world has been turned upside down by the coronavirus pandemic, the virus poses an increased threat to people with Parkinson’s disease (PD). Having a compromised immune system, particularly involving the lungs, means people with PD are at higher risk of some of the more dangerous complications of COVID-19. So, this seems like an appropriate time for CIRM to hold a special Facebook Live “Ask the Stem Cell Team” About Parkinson’s disease.

We are holding the event on Tuesday, May 5th at noon PDT.

The initial reason for the Facebook Live was the CIRM Board approving almost $8 million for Dr. Krystof Bankiewicz at Brain Neurotherapy Bio, Inc. to run a Phase 1 clinical trial targeting PD. Dr. Bankiewicz is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating PD symptoms and potentially slowing down the disease progress.

Dr. Bankiewicz will be joined by two of CIRM’s fine Science Officers, Dr. Lila Collins and Dr. Kent Fitzgerald. They’ll talk about the research targeting Parkinson’s that CIRM is funding plus other promising research taking place.

And we are delighted to have a late addition to the team. Our CIRM Board member and patient advocate for Parkinson’s disease, Dr. David Higgins. David has a long history of advocacy for PD and adds the invaluable perspective of someone living with PD.

As always, we want this to be as interactive as possible, so we want to get your questions. You can do this on the day, posting them alongside the live feed, or you can send them to us ahead of time at info@cirm.ca.gov. We’ll do our best to answer as many as we can on the day, and those we don’t get to during the broadcast we’ll answer in a later blog.

We look forward to seeing you there.