Stem Cell Agency Board Invests in 19 Discovery Research Programs Targeting Cancers, Heart Disease and Other Disorders

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Dr. Judy Shizuru, Stanford University

While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.

The awards are from CIRM’s DISC2 Quest program, which supports  the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.

“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”

Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.

Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics

Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.

Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.

In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.

Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.

Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.

The full list of DISC2 Quest awards is:

APPLICATION NUMBERTITLE OF PROGRAMPRINCIPAL INVESTIGATORAMOUNT
  DISC2-13400  Targeted Immunotherapy-Based Blood Stem Cell Transplantation    Judy Shizuru, Stanford Universtiy  $1,341,910    
  DISC2-13505  Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells    Lili Yang, UCLA  $1,404,000
  DISC2-13515  A treatment for Rett syndrome using glial-restricted
neural progenitor cells  
  Alysson Muotri, UC San Diego  $1,402,240    
  DISC2-13454  Targeting pancreatic cancer stem cells with DDR1 antibodies.    Michael Karin, UC San Diego  $1,425,600  
  DISC2-13483  Enabling non-genetic activity-driven maturation of iPSC-derived neurons    Alex Savtchenko, Nanotools Bioscience  $675,000
  DISC2-13405  Hematopoietic Stem Cell Gene Therapy for Alpha
Thalassemia  
  Don Kohn, UCLA    $1,323,007  
    DISC2-13507  CAR T cells targeting abnormal N-glycans for the
treatment of refractory/metastatic solid cancers  
  Michael Demetriou, UC Irvine  $1,414,800  
  DISC2-13463  Drug Development of Inhibitors of Inflammation Using
Human iPSC-Derived Microglia (hiMG)  
  Stuart Lipton, Scripps Research Inst.  $1,658,123  
  DISC2-13390  Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure    Timothy Hoey, Tenaya Therapeutics  $1,215,000  
  DISC2-13417  AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder    Kyle Fink, UC Davis  $1,429,378  
  DISC2-13415  Defining the Optimal Gene Therapy Approach of
Human Hematopoietic Stem Cells for the Treatment of
Dedicator of Cytokinesis 8 (DOCK8) Deficiency  
  Caroline Kuo, UCLA  $1,386,232  
  DISC2-13498  Bioengineering human stem cell-derived beta cell
organoids to monitor cell health in real time and improve therapeutic outcomes in patients  
  Katy Digovich, Minutia, Inc.  $1,198,550  
  DISC2-13469  Novel antisense therapy to treat genetic forms of
neurodevelopmental disease.  
  Joseph Gleeson, UC San Diego  $1,180,654  
  DISC2-13428  Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)    Michael Bollong, Scripps Research Inst.  $1,244,160  
  DISC2-13456  Novel methods to eliminate cancer stem cells    Dinesh Rao, UCLA  $1,384,347  
  DISC2-13441  A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in
pediatric patients with Crohn’s diseas  
  Robert Barrett Cedars-Sinai  $776,340
  DISC2-13512  Modified RNA-Based Gene Therapy for Cardiac
Regeneration Through Cardiomyocyte Proliferation
  Deepak Srivastava, Gladstone Institutes  $1,565,784
  DISC2-13510  An hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly
neutralizing antibodies  
  Brian Lawson, The Scintillon Institute  $1,143,600  
  DISC2-13475  Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model    Xian-Jie Yang, UCLA  $1,345,691  

HOPE for patients with a muscle destroying disease

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Caleb Sizemore, photo by Todd Dubnicoff

Caleb Sizemore says growing up with Duchenne’s Muscular Dystrophy (DMD) was tough. The disease is a rare genetic disorder that slowly destroys a person’s muscles, impairing their ability to walk or breathe. Eventually it attacks the heart leading to premature death.

Caleb says the disease meant “I was limited in what I could do, where I couldn’t play sports and where I was teased and bullied sometimes for being different.”

In the past people with DMD – almost all of whom are boys – lost the ability to walk by the age of 12, and many died in their 20’s. But a new treatment – originally funded by CIRM – is showing promise in helping reverse some of the damage caused by the disease.

Dr. Craig McDonald working with a person who has DMD: Photo courtesy UC Davis

Results from a clinical trial – published in the journal Lancet – showed that the therapy helped halt the decline in muscle strength in the arms and hands, and in MRI’s appeared to improve heart function.

In a news release, Dr. Craig McDonald, a UC Davis professor and the lead author of the study, said: “The trial produced statistically significant and unprecedented stabilization of both skeletal muscle deterioration affecting the arms and heart deterioration of structure and function in non-ambulatory DMD patients.”

The therapy, called CAP-1002, uses cells derived from the human heart that have previously demonstrated the ability to reduce muscle inflammation and enhance cell regeneration. The clinical trial, called HOPE-2 (Halt cardiomyopathy progression in Duchenne).

Dr. McDonald says with current treatments only having a limited impact on the disease, CAP-1002 may have a big impact on the people affected by DMD and their families.

“The trial showed consistent benefits of this cell-based therapy. It suggests that this infusion may be an important treatment option for the boys and young men who have this debilitating disorder.”

The team now hope to be able to apply to the Food and Drug Administration for permission to start a bigger clinical trial involving more patients.

Caleb Sizemore took part in an earlier clinical trial involving this approach. He says MRI’s showed that the therapy appeared to reduce scarring on his heart and gave him greater energy.

In 2017 Caleb talked to the CIRM governing Board about DMD and his part in the clinical trial. You can see that video here.

Joining the movement to fight rare diseases

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It’s hard to think of something as being rare when it affects up to 30 million Americans and 300 million people worldwide. But the truth is there are more than 6,000 conditions – those affecting 200,000 people or fewer – that are considered rare.  

Today, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called or orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.

At the California Institute for Regenerative Medicine (CIRM), we have no such reservations. In fact last Friday our governing Board voted to invest almost $12 million to support a clinical trial for IPEX syndrome. IPEX syndrome is a condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. This leads to the development of Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive. It’s diagnosed in infancy, most of those affected are boys, and it is often fatal.

Taylor Lookofsky (who has IPEX syndrome) and his father Brian

IPEX is one of two dozen rare diseases that CIRM is funding a clinical trial for. In fact, more than one third of all the projects we fund target a rare disease or condition. Those include:

Some might question the wisdom of investing hundreds of millions of dollars in conditions that affect a relatively small number of patients. But if you see the faces of these patients and get to know their families, as we do, you know that often agencies like CIRM are their only hope.

Dr. Maria Millan, CIRM’s President and CEO, says the benefits of one successful approach can often extend far beyond one rare disease.

“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives. Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders.”

CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.

A personal reason to develop a better gene therapy

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Credit : Allison Dougherty, Broad Communications

For Sharif Tabebordbar, finding a gene therapy for genetic muscle wasting diseases was personal. When he was a teenager, his father was diagnosed with a rare genetic muscle disease that eventually left him unable to walk.

In an interview with the Broad Institute at MIT he said: “I watched my dad get worse and worse each day. It was a huge challenge to do things together as a family – genetic disease is a burden on not only patients but families. I thought: This is very unfair to patients and there’s got to be a way to fix this. That’s been my motivation during the 10 years that I’ve been working in the field of gene therapy.”

That commitment now seems to be paying off. In a study published in the journal Cell, Tabebordar and his team at MIT and Harvard showed how they have developed a new, safer and easier way to deliver genes to help repair wasting muscles.   

In earlier treatments targeting genetic muscle diseases, researchers used a virus to help deliver the gene that would correct the problem. However, to be effective they had to use high doses of the gene-carrying virus to ensure it reached as many muscles throughout the body as possible. But this meant that more of the payload often ended up in the liver and that led to severe side effects in some patients, even a few deaths.

The usual delivery method of these gene-correcting therapies is something called an adeno-associated virus (AAV), so Dr. Tabebordar set out to develop a new kind of AAV, one that would be safer for patients and more effective at tackling the muscle wasting.

They started by taking an adeno-associated virus called AAV9 and then set out about tweaking its capsid – that’s the outer shell that helps protect the virus and allows it to attach to another cell and penetrate it to deliver the corrected gene. They called this new viral vector MyoAAV and in tests it quickly showed it had an enhanced ability to deliver genes into cells.

The team showed that it not only was around 10 times more efficient at reaching muscle than other AAVs, but that it also reduces the amount that reaches the liver. This meant that MyoAAV could achieve impressive results in doses up to 250 times lower than those previously used.

In animal studies MyoAAV showed encouraging results in diseases like Duchenne Muscular Dystrophy and X-linked myotubular myopathy. Dr. Amy Wagers, a co-senior author of the study, says they are hopeful it will be equally effective in people.

“All of these results demonstrate the broad applicability of the MyoAAV vectors for delivery to muscle. These vectors work in different disease models and across different ages, strains and species, which demonstrates the robustness of this family of AAVs. We have an enormous amount of information about this class of vectors from which the field can launch many exciting new studies.”

Repairing damaged muscles

Close-up of the arm of a 70-year-old male patient with a torn biceps muscle as a result of a bowling injury; Photo courtesy Science Photo Library

In the time of coronavirus an awful lot of people are not just working from home they’re also working out at home. That’s a good thing; exercise is a great way to boost the immune system, stay healthy and deal with stress. But for people used to more structured workouts at the gym it can come with a downside. Trying new routines at home that look easy on YouTube, but are harder in practice could potentially increase the risk of injury.

A new study from Japan looks at what happens when you damage a muscle. It won’t help it heal faster, but it will at least let you understand what is happening inside your body as you sit there with ice on your arm and ibuprofen in your hand.

The researchers found that when you damage a muscle, for example by trying to lift too much weight or doing too many repetitions of one exercise, the damaged muscle fibers leak substances that activate nearby “satellite” stem cells. These satellite cells then flock to the site of the injury and help repair the muscle.

The team, from Kumamoto University and Nagasaki University in Japan, named the leaking substances “Damaged myofiber-derived factors” (DMDFs) – personally I think “Substances Leaked by Injured Muscles (SLIM) would be a much cooler acronym, but that’s just me. Gaining a deeper understanding of how DMDFs work might help lead to therapies for older people who have fewer satellite muscle cells, and also for conditions like muscular dystrophy and age-related muscular fragility (sarcopenia), where the number and function of satellite cells decreases.

In an article in Science Daily, Professor Yusuke Ono, the leader of the study, says it’s possible that DMDFs play an even greater role in the body:

“In this study, we proposed a new muscle injury-regeneration model. However, the detailed molecular mechanism of how DMDFs activate satellite cells remains an unclear issue for future research. In addition to satellite cell activation, DMDF moonlighting functions are expected to be diverse. Recent studies have shown that skeletal muscle secretes various factors that affect other organs and tissues, such as the brain and fat, into the bloodstream, so it may be possible that DMDFs are involved in the linkage between injured muscle and other organs via blood circulation. We believe that further elucidation of the functions of DMDFs could clarify the pathologies of some muscle diseases and help in the development of new drugs.”

The study appears in the journal Stem Cell Reports.

Partners in health

From left to right: Heather Dahlenburg, Jan Nolta, Jeannine Logan White, Sheng Yang
From left to right: Heather Dahlenburg, staff research associate; Jan Nolta, director of the Stem Cell Program; Jeannine Logan White, advanced cell therapy project manager; Sheng Yang, graduate student, Bridges Program, Humboldt State University, October 18, 2019. (AJ Cheline/UC Davis)

At CIRM we are modest enough to know that we can’t do everything by ourselves. To succeed we need partners. And in UC Davis we have a terrific partner. The work they do in advancing stem cell research is exciting and really promising. But it’s not just the science that makes them so special. It’s also their compassion and commitment to caring for patients.

What follows is an excerpt from an article by Lisa Howard on the work they do at UC Davis. When you read it you’ll see why we are honored to be a part of this research.

Gene therapy research at UC Davis

UC Davis’ commitment to stem cell and gene therapy research dates back more than a decade.

In 2010, with major support from the California Institute for Regenerative Medicine (CIRM), UC Davis launched the UC Davis Institute for Regenerative Cures, which includes research facilities as well as a Good Manufacturing Practice (GMP) facility.

In 2016, led by Fred Meyers, a professor in the School of Medicine, UC Davis launched the Center for Precision Medicine and Data Sciences, bringing together innovations such as genomics and biomedical data sciences to create individualized treatments for patients.

Last year, the university launched the Gene Therapy Center, part of the IMPACT Center program.

Led by Jan Nolta, a professor of cell biology and human anatomy and the director of the UC Davis Institute for Regenerative Cures, the new center leverages UC Davis’ network of expert researchers, facilities and equipment to establish a center of excellence aimed at developing lifelong cures for diseases.

Nolta began her career at the University of Southern California working with Donald B. Kohn on a cure for bubble baby disease, a condition in which babies are born without an immune system. The blood stem cell gene therapy has cured more than 50 babies to date.

Work at the UC Davis Gene Therapy Center targets disorders that potentially can be treated through gene replacement, editing or augmentation.

“The sectors that make up the core of our center stretch out across campus,” said Nolta. “We work with the MIND Institute a lot. We work with the bioengineering and genetics departments, and with the Cancer Center and the Center for Precision Medicine and Data Sciences.”

A recent UC Davis stem cell study shows a potential breakthrough for healing diabetic foot ulcers with a bioengineered scaffold made up of human mesenchymal stem cells (MSCs). Another recent study revealed that blocking an enzyme linked with inflammation enables stem cells to repair damaged heart tissue. A cell gene therapy study demonstrated restored enzyme activity in Tay-Sachs disease affected cells in humanized mouse models.

Several cell and gene therapies have progressed to the point that ongoing clinical trials are being conducted at UC Davis for diseases, including sickle-cell anemia, retinopathy, muscle injury, dysphasia, advanced cancer, and Duchenne muscular dystrophy, among others.

“Some promising and exciting research right now at the Gene Therapy Center comes from work with hematopoietic stem cells and with viral vector delivery,” said Nolta.

Hematopoietic stem cells give rise to other blood cells. A multi-institutional Phase I clinical trial using hematopoietic stem cells to treat HIV-lymphoma patients is currently underway at UC Davis.

.Joseph Anderson

Joseph Anderson

“We are genetically engineering a patient’s own blood stem cells with genes that block HIV infection,” said Joseph Anderson, an associate professor in the UC Davis Department of Internal Medicine. The clinical trial is a collaboration with Mehrdad Abedi, the lead principal investigator.

“When the patients receive the modified stem cells, any new immune system cell, like T-cell or macrophage, that is derived from one of these stem cells, will contain the HIV-resistant genes and block further infection,” said Anderson.

He explained that an added benefit with the unique therapy is that it contains an additional gene that “tags” the stem cells. “We are able to purify the HIV-resistant cells prior to transplantation, thus enriching for a more protective cell population.

Kyle David Fink

Kyle David Fink

Kyle David Fink, an assistant professor of neurology at UC Davis, is affiliated with the Stem Cell Program and Institute for Regenerative Cures. His lab is focused on leveraging institutional expertise to bring curative therapies to rare, genetically linked neurological disorders.

“We are developing novel therapeutics targeted to the underlying genetic condition for diseases such as CDKL5 deficiency disorder, Angelman, Jordan and Rett syndromes, and Juvenile Huntington’s disease,” said Fink.

The lab is developing therapies to target the underlying genetic condition using DNA-binding domains to modify gene expression in therapeutically relevant ways. They are also creating novel delivery platforms to allow these therapeutics to reach their intended target: the brain.

“The hope is that these highly innovative methods will speed up the progress of bringing therapies to these rare neurodegenerative disease communities,” said Fink.Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program.

Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program, October 18, 2019. (AJ Cheline/UC Davis)

Developing potential lifetime cures

Among Nolta’s concerns is how expensive gene therapy treatments can be.

“Some of the therapies cost half a million dollars and that’s simply not available to everyone. If you are someone with no insurance or someone on Medicare, which reimburses about 65 percent, it’s harder for you to get these life-saving therapies,” said Nolta.

To help address that for cancer patients at UC Davis, Nolta has set up a team known as the “CAR T Team.”

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy in which a patient’s own immune cells are reprogrammed to attack a specific protein found in cancer cells.

“We can develop our own homegrown CAR T-cells,” said Nolta. “We can use our own good manufacturing facility to genetically engineer treatments specifically for our UC Davis patients.”

Although safely developing stem cell treatments can be painfully slow for patients and their families hoping for cures, Nolta sees progress every day. She envisions a time when gene therapy treatments are no longer considered experimental and doctors will simply be able to prescribe them to their patients.

“And the beauty of the therapy is that it can work for the lifetime of a patient,” said Nolta.

CIRM-funded kidney transplant procedure eyeing faster approval

Kidney transplant surgery.

Medeor Therapeutics, which is running a CIRM-funded clinical trial to help people getting kidney transplants, just got some really good news. The US Food and Drug Administration (FDA) has just granted their product Regenerative Medicine Advanced Therapy (RMAT) designation. That’s a big deal because it means they may be able to apply for faster review and approval and get their therapy to more patients faster.

Here’s why that RMAT designation matters.

Over 650,000 Americans suffer from end-stage kidney disease – a life-threatening condition caused by the loss of kidney function. The best available treatment for these patients is a kidney transplant from a genetically matched living donor. However, patients who receive a transplant must take life-long immunosuppressive drugs to prevent their immune system from rejecting the transplanted organ. Over time, these drugs are toxic and can increase a patient’s risk of infection, heart disease, cancer and diabetes.  Despite these drugs, many patients still lose transplanted organs due to rejection.

To tackle this problem Medeor is developing a stem cell-based therapy called MDR-101. This is being tested in a Phase 3 clinical trial and it’s hoped it will eliminate the need for immunosuppressive drugs in genetically matched kidney transplant patients.

The company takes blood-forming stem cells and immune cells from the organ donor and infuses them into the patient receiving the donor’s kidney. Introducing the donor’s immune cells into the patient creates a condition called “mixed chimerism” where immune cells from the patient and the donor are able to co-exist. In this way, the patient’s immune system is able to adapt to and tolerate the donor’s kidney, potentially eliminating the need for the immunosuppressive drugs that are normally necessary to prevent transplant rejection.

So how does getting RMAT designation help that? Well, the FDA created the RMAT program to help speed up the development and review of regenerative medicine therapies that can treat, modify, reverse, or cure a serious condition. If MDR-101shows it is both safe and effective RMAT could help it get faster approval for wider use.

In a news release Giovanni Ferrara, President and CEO of Medeor, welcomed the news.

“This important designation underscores the tremendous unmet medical need for alternatives to today’s immunosuppressive therapies for transplantation. We have the potential to help people live longer, healthier lives without the need for high dose and chronic immunosuppression and we thank the FDA for this designation that will assist us progressing as efficiently as possible toward a commercially available product.”

This is the seventh CIRM-supported project that has been granted RMAT designation. The others are jCyte, Lineage, Humacyte, St. Jude’s/UCSF X-linked SCID, Poseida, Capricor

Perseverance: from theory to therapy. Our story over the last year – and a half

Some of the stars of our Annual Report

It’s been a long time coming. Eighteen months to be precise. Which is a peculiarly long time for an Annual Report. The world is certainly a very different place today than when we started, and yet our core mission hasn’t changed at all, except to spring into action to make our own contribution to fighting the coronavirus.

This latest CIRM Annual Reportcovers 2019 through June 30, 2020. Why? Well, as you probably know we are running out of money and could be funding our last new awards by the end of this year. So, we wanted to produce as complete a picture of our achievements as we could – keeping in mind that we might not be around to produce a report next year.

Dr. Catriona Jamieson, UC San Diego physician and researcher

It’s a pretty jam-packed report. It covers everything from the 14 new clinical trials we have funded this year, including three specifically focused on COVID-19. It looks at the extraordinary researchers that we fund and the progress they have made, and the billions of additional dollars our funding has helped leverage for California. But at the heart of it, and at the heart of everything we do, are the patients. They’re the reason we are here. They are the reason we do what we do.

Byron Jenkins, former Naval fighter pilot who battled back from his own fight with multiple myeloma

There are stories of people like Byron Jenkins who almost died from multiple myeloma but is now back leading a full, active life with his family thanks to a CIRM-funded therapy with Poseida. There is Jordan Janz, a young man who once depended on taking 56 pills a day to keep his rare disease, cystinosis, under control but is now hoping a stem cell therapy developed by Dr. Stephanie Cherqui and her team at UC San Diego will make that something of the past.

Jordan Janz and Dr. Stephanie Cherqui

These individuals are remarkable on so many levels, not the least because they were willing to be among the first people ever to try these therapies. They are pioneers in every sense of the word.

Sneha Santosh, former CIRM Bridges student and now a researcher with Novo Nordisk

There is a lot of information in the report, charting the work we have done over the last 18 months. But it’s also a celebration of everyone who made it possible, and our way of saying thank you to the people of California who gave us this incredible honor and opportunity to do this work.

We hope you enjoy it.

Two rare diseases, two pieces of good news

Dr. Stephanie Cherqui

Last week saw a flurry of really encouraging reports from projects that CIRM has supported. We blogged about two of them last Wednesday, but here’s another two programs showing promising results.

UC San Diego researcher Dr. Stephanie Cherqui is running a CIRM-funded clinical trial for cystinosis. This is a condition where patients lack the ability to clear an amino acid called cystine from their cells. As the cystine builds up it can lead to multi-organ failure affecting the kidneys, eyes, thyroid, muscle, and pancreas.

Dr. Cherqui uses the patient’s own blood stem cells, that have been genetically corrected in the lab to remove the defective gene that causes the problem. It’s hoped these new cells will help reduce the cystine buildup.

The data presented at the annual meeting of the American Society of Cell and Gene Therapy (ASCGT) focused on the first patient treated with this approach. Six months after being treated the patient is showing positive trends in kidney function. His glomerular filtration rate (a measure of how well the kidneys are working) has risen from 38 (considered a sign of moderate to severe loss of kidney function) to 52 (mild loss of kidney function). In addition, he has not had to take the medication he previously needed to control the disorder, nor has he experienced any serious side effects from the therapy.

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Dr. Linda Marban of Capricor

Capricor Therapeutics also had some positive news about its therapy for people with Duchenne’s Muscular Dystrophy (DMD). This is a progressive genetic disorder that slowly destroys the muscles. It affects mostly boys. By their teens many are unable to walk, and most die of heart or lung failure in their 20’s. 

Capricor is using a therapy called CAP-1002, using cells derived from heart stem cells, in the HOPE-2 clinical trial.

In a news release Capricor said 12-month data from the trial showed improvements in heart function, lung function and upper body strength. In contrast, a placebo control group that didn’t get the CAP-1002 treatment saw their condition deteriorate.

Craig McDonald, M.D., the lead investigator on the study, says these results are really encouraging.  “I am incredibly pleased with the outcome of the HOPE-2 trial which demonstrated clinically relevant benefits of CAP-1002 which resulted in measurable improvements in upper limb, cardiac and respiratory function. This is the first clinical trial which shows benefit to patients in advanced stages of DMD for which treatment options are limited.”

You can read the story of Caleb Sizemore, one of the patients treated in the CIRM-funded portion of this trial.

Treatment for heart failure shows promising results for COVID-19 patients

Dr. Linda Marbán

To help with the coronavirus pandemic, many scientists are repurposing previously developed approaches or treatments to see if they can be used to treat patients with COVID-19. Capricor Therapeutics, lead by Dr. Linda Marbán, is using cardiosphere derived cells (CDCs), which are stem cells derived from heart tissue, to treat critically ill patients with COVID-19.

When a patient contracts the virus, their body produces cytokines, proteins that play an important role in the immune response. Unfortunately, having too many cytokines, known as a “cytokine storm”, leads to a severe immune reaction that can cause pneumonia, organ failure, and death. CDCs in previous studies have been shown to help regulate the immune response and cytokines, which could help patients with COVID-19.

Over the course of one month, six critically ill patients with COVID-19, five of whom were on mechanical ventilators, were treated with CDCs. In these compassionate care cases, five male patients and one female patient received treatment. Of the five patients on ventilator support, four patients no longer required ventilator support within just one to four days after treatment. Although these results are promising, it is important to remember that this treatment is in very early testing and will need to demonstrate significant improvement in larger patient groups.

Following a review of the results of this small study, the U.S. Food and Drug Administration (FDA) approved treatment of up to an 20 additional COVID-19 patients.

In a press release, Dr. Marbán discuses the results of the compassionate care study and treatment of additional COVID-19 patients.

“As the global medical community continues to come together in its battle against COVID-19, the results of our initial compassionate care cases are extremely promising and what we had anticipated. We look forward to continuing to treat additional patients under our recently approved expanded access program Investigational New Drug application.” 

The treatment used was developed with the help of a CIRM funded preclinical study. It has also been used in three CIRM funded clinical trials for heart disease associated with duchenne muscular dystrophy, heart failure, and pulmonary arterial hypertension.