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  

Can regenerative medicine turn back the clock on aging?

One of my favorite phrases is “standing room only”. I got a chance to use it last week when we held a panel discussion on whether regenerative medicine could turn back the clock on aging. The event was at the annual conference of the International Society for Stem Cell Research (ISSCR) and more than 150 people packed into a conference room to hear the debate (so far more than 800 also watched a live stream of the event.)

It’s not surprising the place was jammed. The speakers included:

  • Dr. Deepak Srivastava, the President of the Gladstone Institutes, an expert on heart disease and the former President of ISSCR.
  • Dr. Stanley “Tom” Carmichael, Chair of the Department of Neurology at UCLA and an expert on strokes and other forms of brain injury.
  • Adrienne Shapiro, the mother of a daughter with sickle cell disease, a tireless patient advocate and supporter of regenerative medicine research, and the co-founder of Axis Advocacy, a family support organization for people with sickle cell.
  • Jonathan Tomas, PhD, JD, the Chair of the CIRM Board.

And the topic is a timely one. It is estimated that as many as 90 percent of the people who die every day, die from diseases of aging such as heart disease, stroke, and cancer. So, what can be done to change that, to not just slow down or stop these diseases, but to turn back the clock, to repair the damage already done and replace cells and tissues already destroyed.

The conversation was enlightening, hopeful and encouraging, but also cautionary.

You can watch the whole event on our Youtube channel.

I think you are going to enjoy it.

Join us to hear how stem cell and gene therapy are taking on diseases of aging

It is estimated that as many as 90 percent of people in industrialized countries who die every day, die from diseases of aging such as heart disease, stroke, and cancer. Of those still alive the numbers aren’t much more reassuring. More than 80 percent of people over the age of 65 have a chronic medical condition, while 68 percent have two or more.

Current medications can help keep some of those conditions, such as high blood pressure, under control but regenerative medicine wants to do a lot more than that. We want to turn back the clock and restore function to damaged organs and tissues and limbs. That research is already underway and we are inviting you to a public event to hear all about that work and the promise it holds.

On June 16th from 3p – 4.30p PST we are holding a panel discussion exploring the impact of regenerative medicine on aging. We’ll hear from experts on heart disease and stroke; we will look at other ground breaking research into aging; and we’ll discuss the vital role patients and patient advocates play in helping advance this work.

The discussion is taking place in San Francisco at the annual conference of the International Society for Stem Cell Research. But you can watch it from the comfort of your own home. That’s because we are going to live stream the event.

Here’s where you can see the livestream: https://www.youtube.com/watch?v=CaUgsc5alDI

And if you have any questions you would like the panel to answer feel free to send them to us at info@cirm.ca.gov

Smoking marijuana could be bad for your heart, but there is an unusual remedy

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Smoking medical marijuana: Photo courtesy Elsa Olofsson

Millions of Americans use marijuana for medical reasons, such as reducing anxiety or helping ease the side effects of cancer therapy. Millions more turn to it for recreational reasons, saying it helps them relax. Now a new study says those who smoke marijuana regularly might be putting themselves at increased risk of heart disease and heart attack.

There has long been debate about the benefits versus the risks for using cannabis, with evidence on both sides to support each position. For example some studies have shown taking oral cannabinoids can help people cope with the nausea brought on by chemotherapy. Other studies have shown that regular use of marijuana can cause problems such as marijuana use disorder, a condition where the user is showing physical or psychological problems but has difficulty controlling or reducing their use of cannabis.

Now this latest study, from researchers at Stanford Medicine,  shows that THC, the psychoactive part of the drug, can cause inflammation in endothelial cells. These are the cells that line the interior of blood vessels. When these cells become inflamed it can cause a constriction of the vessels and reduce blood flow. Over time this can create conditions that increase the risk of heart disease and heart attack.

The researchers, led by Dr. Joe Wu, began by analyzing data from the UK Biobank. This included information about some 35,000 people who reported smoking marijuana. Of these around 11,000 smoked more than once a month. The researchers found that regular marijuana smokers:

  • Were significantly more likely than others to have a heart attack.
  • Were also more likely to have their first heart attack before the age of 50, increasing their risk of subsequent attacks.

The team then used the iPSC method to create human endothelial cells and, in the lab, found that THC appeared to promote inflammation in the cells. They also found signs it created early indications of atherosclerosis, where there is a buildup of fat and plaque in the arteries.

They then tested mice which had been bred to have high levels of cholesterol and who were given a high fat diet. Some of the mice were then injected with THC, at a level comparable to smoking one marijuana cigarette a day. Those mice had far larger amounts of atherosclerosis plaque in their arteries compared to the mice who didn’t get the THC.

In a news release, Dr.Wu, the lead author of the study, said: “There’s a growing public perception that marijuana is harmless or even beneficial. Marijuana clearly has important medicinal uses, but recreational users should think carefully about excessive use.”

On the bright side, the team also reported that the damage caused by THC can be stopped by genistein, a naturally occurring compound found in soy and fava beans. The study, in the journal Cell, also found that genistein blocked the bad impact of THC without impeding the good impacts.

“As more states legalize the recreational use of marijuana, users need to be aware that it could have cardiovascular side effects,” said Dr. Wu. “But genistein works quite well to mitigate marijuana-induced damage of the endothelial vessels without blocking the effects marijuana has on the central nervous system, and it could be a way for medical marijuana users to protect themselves from a cardiovascular standpoint.”

Two Early-Stage Research Programs Targeting Cartilage Damage Get Funding from Stem Cell Agency

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Darryl D’Lima: Scripps Health

Every year millions of Americans suffer damage to their cartilage, either in their knee or other joints, that can eventually lead to osteoarthritis, pain and immobility. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two projects targeting repair of damaged cartilage.

The projects were among 17 approved by CIRM as part of the DISC2 Quest Discovery Program. The program promotes 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.

Dr. Darryl D’Lima and his team at Scripps Health were awarded $1,620,645 to find a way to repair a torn meniscus. Every year around 750,000 Americans experience a tear in their meniscus, the cartilage cushion that prevents the bones in the knee grinding against each other. These injuries accelerate the early development of osteoarthritis, for which there is no effective treatment other than total joint replacement, which is a major operation. There are significant socioeconomic benefits to preventing disabling osteoarthritis. The reductions in healthcare costs are also likely to be significant.

The team will use stem cells to produce meniscal cells in the lab. Those are then seeded onto a scaffold made from collagen fibers to create tissue that resembles the knee meniscus. The goal is to show that, when placed in the knee joint, this can help regenerate and repair the damaged tissue.

This research is based on an earlier project that CIRM funded. It highlights our commitment to helping good science progress, hopefully from the bench to the bedside where it can help patients.

Dr. Kevin Stone: Photo courtesy Stone Research Foundation

Dr. Kevin Stone and his team at The Stone Research Foundation for Sports Medicine and Arthritis were awarded $1,316,215 to develop an approach to treat and repair damaged cartilage using a patient’s own stem cells.

They are using a paste combining the patient’s own articular tissue as well as Mesenchymal Stem Cells (MSC) from their bone marrow. This mixture is combined with an adhesive hydrogel to form a graft that is designed to support cartilage growth and can also stick to surfaces without the need for glue. This paste will be used to augment the use of a microfracture technique, where micro-drilling of the bone underneath the cartilage tear brings MSCs and other cells to the fracture site. The hope is this two-pronged approach will produce an effective and functional stem cell-based cartilage repair procedure.

If effective this could produce a minimally invasive, low cost, one-step solution to help people with cartilage injuries and arthritis.

The full list of DISC2 grantees is:

ApplicationTitlePrincipal Investigator and InstitutionAmount
DISC2-13212Preclinical development of an exhaustion-resistant CAR-T stem cell for cancer immunotherapy  Ansuman Satpathy – Stanford University    $ 1,420,200  
DISC2-13051Generating deeper and more durable BCMA CAR T cell responses in Multiple Myeloma through non-viral knockin/knockout multiplexed genome engineering  Julia Carnevale – UC San Francisco  $ 1,463,368  
DISC2-13020Injectable, autologous iPSC-based therapy for spinal cord injury  Sarah Heilshorn – Stanford University    $789,000
DISC2-13009New noncoding RNA chemical entity for heart failure with preserved ejection fraction.  Eduardo Marban – Cedars-Sinai Medical Center  $1,397,412  
DISC2-13232Modulation of oral epithelium stem cells by RSpo1 for the prevention and treatment of oral mucositis  Jeffrey Linhardt – Intact Therapeutics Inc.  $942,050  
DISC2-13077Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)  Mathew Blurton-Jones – UC Irvine    $1,199,922  
DISC2-13201Matrix Assisted Cell Transplantation of Promyogenic Fibroadipogenic Progenitor (FAP) Stem Cells  Brian Feeley – UC San Francisco  $1,179,478  
DISC2-13063Improving the efficacy and tolerability of clinically validated remyelination-inducing molecules using developable combinations of approved drugs  Luke Lairson – Scripps Research Inst.  $1,554,126  
DISC2-13213Extending Immune-Evasive Human Islet-Like Organoids (HILOs) Survival and Function as a Cure for T1D  Ronald Evans – The Salk Institute for Biological Studies    $1,523,285  
DISC2-13136Meniscal Repair and Regeneration  Darryl D’Lima – Scripps Health      $1,620,645  
DISC2-13072Providing a cure for sphingosine phosphate lyase insufficiency syndrome (SPLIS) through adeno-associated viral mediated SGPL1 gene therapy  Julie Saba – UC San Francisco  $1,463,400  
DISC2-13205iPSC-derived smooth muscle cell progenitor conditioned medium for treatment of pelvic organ prolapse  Bertha Chen – Stanford University  $1,420,200  
DISC2-13102RNA-directed therapy for Huntington’s disease  Gene Wei-Ming Yeo  – UC San Diego  $1,408,923  
DISC2-13131A Novel Therapy for Articular Cartilage Autologous Cellular Repair by Paste Grafting  Kevin Stone – The Stone Research Foundation for Sports Medicine and Arthritis    $1,316,215  
DISC2-13013Optimization of a gene therapy for inherited erythromelalgia in iPSC-derived neurons  Ana Moreno – Navega Therapeutics    $1,157,313  
DISC2-13221Development of a novel stem-cell based carrier for intravenous delivery of oncolytic viruses  Edward Filardo – Cytonus Therapeutics, Inc.    $899,342  
DISC2-13163iPSC Extracellular Vesicles for Diabetes Therapy  Song Li – UC Los Angeles  $1,354,928  

How two California researchers are advancing world class science to develop real life solutions

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In our recently launched 5-year Strategic Plan, the California Institute for Regenerative Medicine (CIRM) profiled two researchers who have leveraged CIRM funding to translate basic biological discoveries into potential real-world solutions for devastating diseases.

Dr. Joseph Wu is director of the Stanford Cardiovascular Institute and the recipient of several CIRM awards. Eleven of them to be exact! Over the past 10 years, Dr. Wu’s lab has extensively studied the application of induced pluripotent stem cells (iPSCs) for cardiovascular disease modeling, drug discovery, and regenerative medicine. 

Dr. Wu’s extensive studies and findings have even led to a cancer vaccine technology that is now being developed by Khloris Biosciences, a biotechnology company spun out by his lab. 

Through CIRM funding, Dr. Wu has developed a process to produce cardiomyocytes (cardiac muscle cells) derived from human embryonic stem cells for clinical use and in partnership with the agency. Dr. Wu is also the principal investigator in the first-in-US clinical trial for treating ischemic heart disease. His other CIRM-funded work has also led to the development of cardiomyocytes derived from human induced pluripotent stem cells for potential use as a patch.

Over at UCLA, Dr. Lili Yang and her lab team have generated invariant Natural Killer T cells (iNKT), a special kind of immune system cell with unique features that can more effectively attack tumor cells. 

More recently, using stem cells from donor cord-blood and peripheral blood samples, Dr. Yang and her team of researchers were able to produce up to 300,000 doses of hematopoietic stem cell-engineered iNKT (HSC–iNKT) cells. The hope is that this new therapy could dramatically reduce the cost of producing immune cell products in the future. 

Additionally, Dr. Yang and her team have used iNKT cells to develop both autologous (using the patient’s own cells), and off-the-shelf anti-cancer therapeutics (using donor cells), designed to target blood cell cancers.

The success of her work has led to the creation of a start-up company called Appia Bio. In collaboration with Kite Pharma, Appia Bio is planning on developing and commercializing the promising technology. 

CIRM has been an avid supporter of Dr. Yang and Dr. Wu’s research because they pave the way for development of next-generation therapies. Through our new Strategic Plan, CIRM will continue to fund innovative research like theirs to accelerate world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and the world.

Visit this page to learn more about CIRM’s new 5-year Strategic Plan and stay tuned as we share updates on our 5-year goals here on The Stem Cellar.

How some brilliant research may have uncovered a potential therapy for Alzheimer’s 

Dr. Nicole Koutsodendris, photo courtesy Gladstone Institutes

In the world of scientific research, the people doing clinical trials tend to suck up all the oxygen in the room. They’re the stars, the ones who are bringing potential therapies to patients. However, there’s another group of researchers who toil away in the background, but who are equally deserving of praise and gratitude. 

Dr. Lana Zholudeva, photo courtesy Gladstone Institutes

These are the scientists who do basic or discovery-level research. This is where all great therapies start. This is where a researcher gets an idea and tests it to see if it holds promise. A good idea and a scientist who asks a simple question, “I wonder if…..”  

Dr. Yadong Huang, Photo courtesy Gladstone Institutes

In our latest “Talking ‘Bout (re)Generation” podcast we talk to three researchers who are asking those questions and getting some truly encouraging answers. They are scientists at the Gladstone Institutes in San Francisco: one seasoned scientist and two young post-docs trying to make a name for themselves. And they might just have discovered a therapy that could help people battling Alzheimer’s disease. 

Enjoy the podcast.


  

Lack of diversity impacts research into Alzheimer’s and dementia

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A National Institutes of Allergy and Infectious Diseases clinical trial admissions coordinator collects information from a volunteer to create a medical record. Credit: NIAID

Alzheimer’s research has been in the news a lot lately, and not for the right reasons. The controversial decision by the Food and Drug Administration (FDA) to approve the drug Aduhelm left many people wondering how, when, or even if it should be used on people battling Alzheimer’s disease. Now a new study is raising questions about many of the clinical trials used to test medications like Aduhelm.

The research, published in the journal Jama Neurology, looked at 302 studies on dementia published in 2018 and 2019. Most of these studies were carried out in North America or Europe, and almost 90 percent of those studied were white.

In an accompanying editorial in the journal, Dr. Cerise Elliott, PhD, of the National Institute on Aging (NIA) in Bethesda, Maryland, and co-authors wrote that this limited the value of the studies: “This, combined with the fact that only 22% of the studies they analyzed even reported on race and ethnicity, and of those, a median 89% of participants were white, reflects the fact that recruitment for research participation is challenging; however, it is unacceptable that studies continue to fail to report participant demographics and that publishers allow such omissions.”

That bias is made all the more glaring by the fact that recent data from the Centers for Disease Control and Prevention shows that among people 65 and older, the Black community has the highest prevalence of Alzheimer’s disease and related dementias (13.8%), followed by Latinx (12.2%), non-Hispanic white (10.3%), American Indian and Alaskan Native (9.1%), and Asian and Pacific Islander (8.4%) populations.

The researchers admitted that the limited sample size – more than 40 percent of the studies they looked at included fewer than 50 patients – could have impacted their findings. Even so this clearly suggests there is a huge divide between the people at greatest risk of developing Alzheimer’s, or some other form of dementia, and the people being studied.

In the editorial, Elliott and his colleagues wrote that without a more diverse and balanced patient population this kind of research: “will continue to underrepresent people most affected by the disease and perpetuate systems that exclude important valuable knowledge about the disease.”


There are more details on this in Medpage Today.

An editorial in the New England Journal of Medicine highlights how this kind of bias is all too common in medical research.

“For years, the Journal has published studies that simply do not include enough participants from the racial and ethnic groups that are disproportionately affected by the illnesses being studied to support any conclusions about their treatment. In the United States, for example, Black Americans have high rates of hypertension and chronic kidney disease, Hispanic Americans have the highest prevalence of nonalcoholic fatty liver disease, Native Americans are disproportionately likely to have metabolic syndrome, and Asian Americans are at particular risk for hepatitis B infection and subsequent cirrhosis, but these groups are frequently underrepresented in clinical trials and cohort studies.”

“For too long, we have tolerated conditions that actively exclude groups from critical resources in health care delivery, research, and education. This exclusion has tragic consequences and undermines confidence in the institutions and the people who are conducting biomedical research. And clinicians cannot know how to optimally prevent and treat disease in members of communities that have not been studied.”

The encouraging news is that, finally, people are recognizing the problem and trying to come up with ways to correct it. The not so encouraging is that it took a pandemic to get us to pay attention.

At CIRM we are committed to being part of the solution. We are now requiring everyone who applies to us for funding to have a written plan on Diversity, Equity and Inclusion, laying out how their work will reflect the diversity of California. We know this will be challenging for all of us. But the alternative, doing nothing, is no longer acceptable.

Stem cell therapy may help mend a broken heart

Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014

Dilated cardiomyopathy (DCM), a condition where the muscles of the heart are weak and can lead to heart failure, is considered rare in children. However, because the symptoms are not always easy to recognize the condition can go unnoticed for many years, and in severe cases can damage the heart irreparably. In that case the child’s only option is a heart transplant, and a lack of organ donors means that is not always available.

Now, new research out of Japan – published in the journal Science Translation Medicine – could lead the way to new treatments to help children avoid the need for a transplant.

In the study, researchers at Okayama University used heart stem cells called cardiosphere-derived cells (CDCs) to try and repair the damage caused by DCM.  

In a news release, lead researcher Professor Hidemasa Oh, says previous work has shown that because CDCs have the ability to turn into heart tissue they have the potential of reversing damage, but it’s not clear if this would work in children.

“I have been working on cardiac regeneration therapy since 2001. In this study, my team and I assessed the safety and efficacy of using CDCs to treat DCM in children.”

Tests in animal models with DCM showed that the CDCs resulted in a thickening of the heart muscle leading to increased blood flow around the body. This increased blood supply helped repair damaged tissue. Based on this trial the researcher determined what might be a suitable dose of CDCs for children with DCM and were granted permission to carry out a Phase 1 clinical trial.

Five young patients were treated and the results were cautiously encouraging. After a year none of the patients had experienced any severe side effects, but all had indications of improved heart function.

The study also gave the researchers some strong clues as to how the therapy seem to work. They found that when the CDCs were transplanted into the patient they secreted exosomes, which play an important role in cells communicating with one another. These exosomes then helped create a series of actions within the body; they blocked further damage to the heart tissue and they also helped kickstart the repair process.

The Okayama team are now hoping to carry out a Phase 2 clinical trial with more patients. Ultimately, they hope to be able to see if this approach could help prevent the need for a heart transplant in children, and even adults.

CIRM funds clinical trials targeting heart disease, stroke and childhood brain tumors

Gary Steinberg (Jonathan Sprague)

Heart disease and stroke are two of the leading causes of death and disability and for people who have experienced either their treatment options are very limited. Current therapies focus on dealing with the immediate impact of the attack, but there is nothing to deal with the longer-term impact. The CIRM Board hopes to change that by funding promising work for both conditions.

Dr. Gary Steinberg and his team at Stanford were awarded almost $12 million to conduct a clinical trial to test a therapy for motor disabilities caused by chronic ischemic stroke.  While “clot busting” therapies can treat strokes in their acute phase, immediately after they occur, these treatments can only be given within a few hours of the initial injury.  There are no approved therapies to treat chronic stroke, the disabilities that remain in the months and years after the initial brain attack.

Dr. Steinberg will use embryonic stem cells that have been turned into neural stem cells (NSCs), a kind of stem cell that can form different cell types found in the brain.  In a surgical procedure, the team will inject the NSCs directly into the brains of chronic stroke patients.  While the ultimate goal of the therapy is to restore loss of movement in patients, this is just the first step in clinical trials for the therapy.  This first-in-human trial will evaluate the therapy for safety and feasibility and look for signs that it is helping patients.

Another Stanford researcher, Dr. Crystal Mackall, was also awarded almost $12 million to conduct a clinical trial to test a treatment for children and young adults with glioma, a devastating, aggressive brain tumor that occurs primarily in children and young adults and originates in the brain.  Such tumors are uniformly fatal and are the leading cause of childhood brain tumor-related death. Radiation therapy is a current treatment option, but it only extends survival by a few months.

Dr. Crystal Mackall and her team will modify a patient’s own T cells, an immune system cell that can destroy foreign or abnormal cells.  The T cells will be modified with a protein called chimeric antigen receptor (CAR), which will give the newly created CAR-T cells the ability to identify and destroy the brain tumor cells.  The CAR-T cells will be re-introduced back into patients and the therapy will be evaluated for safety and efficacy.

Joseph Wu Stanford

Stanford made it three in a row with the award of almost $7 million to Dr. Joe Wu to test a therapy for left-sided heart failure resulting from a heart attack.  The major issue with this disease is that after a large number of heart muscle cells are killed or damaged by a heart attack, the adult heart has little ability to repair or replace these cells.  Thus, rather than being able to replenish its supply of muscle cells, the heart forms a scar that can ultimately cause it to fail.  

Dr. Wu will use human embryonic stem cells (hESCs) to generate cardiomyocytes (CM), a type of cell that makes up the heart muscle.  The newly created hESC-CMs will then be administered to patients at the site of the heart muscle damage in a first-in-human trial.  This initial trial will evaluate the safety and feasibility of the therapy, and the effect upon heart function will also be examined.  The ultimate aim of this approach is to improve heart function for patients suffering from heart failure.

“We are pleased to add these clinical trials to CIRM’s portfolio,” says Maria T. Millan, M.D., President and CEO of CIRM.  “Because of the reauthorization of CIRM under Proposition 14, we have now directly funded 75 clinical trials.  The three grants approved bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures.”