First patient dosed in clinical trial for a drug-resistant form of epilepsy

Tablet BM47753. Neo-Babylonian Period. Courtesy of the British Museum, London.

Epilepsy seems to have been a problem for people for as long as people have been around. The first recorded mention of it is on a 4000-year-old Akkadian tablet found in Mesopotamia (modern day Iraq). The tablet includes a description of a person with “his neck turning left, hands and feet are tense, and his eyes wide open, and from his mouth froth is flowing without him having any consciousness.”

Despite that long history, effective treatments for epilepsy were a long time coming. It wasn’t till the middle of the 19th century that physicians started using bromides to help people with the condition, but they also came with some nasty side effects, including depression, weakness, fatigue, lethargy, and coma.

Fast forward 150 years or so and we are now, hopefully, entering a new era. This week, Neurona Therapeutics announced they had dosed the first patient in their first-in-human clinical trial formesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults. The trial specifically targets people who have a drug-resistant form of MTLE.

Neurona has developed a therapy called NRTX-1001, consisting of a specialized type of neuronal or brain cell derived from embryonic stem cells.  These cells are injected into the brain in the area affected by the seizures where they release a neurotransmitter or chemical messenger that will block the signals in the brain causing the epileptic seizures. Pre-clinical testing suggests a single dose of NRTX-1001 may have a long-lasting ability to suppress seizures.

A new approach is very much needed because current therapies for drug-resistant epilepsy are only partially effective and have serious drawbacks. One treatment that can significantly reduce seizure frequency is the removal of the affected part of the brain, however this can cause serious, irreversible damage, such as impacting memory, mood and vision.

CIRM has a vested interest in seeing this therapy succeed. We have invested more than $14 million over four different awards, in helping this research progress from a basic or Discovery level through to the current clinical trial.

In a news release, two key figures in administering the first dose to a patient said this was an important step forward. 

Harish Babu, M.D., Ph.D., assistant professor of neurosurgery at SUNY Upstate Medical University said: “Neurona’s regenerative cell therapy approach has the potential to provide a single-administration, non-destructive alternative for the treatment of drug-resistant focal epilepsy. Currently, people with mesial temporal lobe epilepsy who are not responsive to anti-seizure medications have few options, such as an invasive surgery that removes or destroys the affected brain tissue.”

Robert Beach, M.D., Ph.D. professor of neurology at SUNY Upstate Medical University added: “The objective of NRTX-1001 is to add cells that have the potential to repair the circuits that are damaged in epilepsy and thus reduce seizure activity.”

There is a huge unmet medical need for an effective, long-term therapy. Right now, it’s estimated that three million Americans have epilepsy, and 25 to 35 percent live with ongoing seizures despite dozens of approved drugs on the market.

If this therapy works it might mean that 4,000 year old tablet will become a medical footnote, rather than a reminder that we still have work to do.

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  

Two reasons to remember June 19th

Today marks two significant events for the Black community. June 19th is celebrated as Juneteenth, the day when federal troops arrived in Galveston, Texas to ensure that the enslaved people there were free. That moment came two and a half years after President Abraham Lincoln signed the Emancipation Proclamation into law.

June 19th is also marked as World Sickle Cell Awareness Day. It’s an opportunity to raise awareness about a disease that affects around 100,000 Americans, most of them Black, and the impact it has on the whole family and entire communities.

Sickle cell disease (SCD) is an inherited blood disorder that is caused by a genetic mutation. Instead of red blood cells being smooth and round and flowing easily through arteries and veins, the cells are sickle shaped and brittle. They can clog up arteries and veins, cutting off blood to vital organs, causing intense pain, organ damage and leading to premature death.

SCD can be cured with a bone marrow transplant, but that’s a risky procedure and most people with SCD don’t have a good match. Medications can help keep it under control but cannot cure it. People with SCD live, on average, 30 years less than a healthy adult.

CIRM has invested almost $60 million in 13 different projects, including five clinical trials, to try and develop a cure for SCD. There are encouraging signs of progress. For example, in July of 2020, Evie Junior took part in a CIRM-funded clinical trial where his own blood stem cells were removed then, in the laboratory, were genetically modified to repair the genetic mutation that causes the disease. Those cells were returned to him, and the hope is they’ll create a sickle cell-free blood supply. Evie hasn’t had any crippling bouts of pain or had to go to the hospital since his treatment.

Evie Junior: Photo by Jaquell Chandler

CIRM has also entered into a unique partnership with the National Heart, Lung and Blood Institute (NHLBI) to co-fund cell and gene therapy programs under the NIH “Cure Sickle Cell” initiative.  The goal is to markedly accelerate the development of cell and gene therapies for SCD.

“There is a real need for a new approach to treating SCD and making life easier for people with SCD and their families,” says Adrienne Shapiro, the mother of a daughter with SCD and the co-founder of Axis Advocacy, a sickle cell advocacy and education organization. “Finding a cure for Sickle Cell would mean that people like my daughter would no longer have to live their life in short spurts, constantly having their hopes and dreams derailed by ER visits and hospital stays.  It would mean they get a chance to live a long life, a healthy life, a normal life.”

We will all keep working together to advance this research and develop a cure. Until then Juneteenth will be a reminder of the work that still lies ahead.

Creating a ‘bespoke’ approach to rare diseases

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Up until recently the word “bespoke” meant just one thing to me, a hand-made suit, customized and fitted to you. There’s a street in London, Saville Row, that specializes in these suits. They’re gorgeous. They’re also very expensive and so I thought I’d never have a bespoke anything.

I was wrong. Because CIRM is now part of a bespoke arrangement. It has nothing to do with suits, it’s far more important than that. This bespoke group is aiming to create tailor-made gene therapies for rare diseases.

It’s called the Bespoke Gene Therapy Consortium (BGTC). Before we go any further I should warn you there’s a lot of acronyms heading your way. The BGTC is part of the Accelerating Medicines Partnership® (AMP®) program. This is a public-private partnership between the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and multiple public and private organizations, such as CIRM.

The program is managed by the Foundation for the NIH (FNIH) and it aims to develop platforms and standards that will speed the development and delivery of customized or ‘bespoke’ gene therapies that could treat the millions of people affected by rare diseases.

Why is it necessary? Well, it’s estimated that there are around 7,000 rare diseases and these affect between 25-30 million Americans. Some of these diseases affect only a few hundred, or even a few dozen people. With so few people they almost always struggle to raise the funds needed to do research to find an effective therapy. However, many of these rare diseases are linked to a mutation or defect in a single gene, which means they could potentially be treated by highly customizable, “bespoke” gene therapy approaches.

Right now, individual disease programs tend to try individual approaches to developing a treatment. That’s time consuming and expensive. The newly formed BGTC believes that if we create a standardized approach, we could develop a template that can be widely used to develop bespoke gene therapies quickly, more efficiently and less expensively for a wide array of rare diseases.

“At CIRM we have funded several projects using gene therapy to help treat, and even cure, people with rare diseases such as severe combined immunodeficiency,” says Dr. Maria T. Millan, the President and CEO of CIRM. “But even an agency with our resources can only do so much. This agreement with the Bespoke Gene Therapy Consortium will enable us to be part of a bigger partnership, one that can advance the field, overcome obstacles and lead to breakthroughs for many rare diseases.”

With gene therapy the goal is to identify the genetic defect that is causing the disease and then deliver a normal copy of the gene to the right tissues and organs in the body, replacing or correcting the mutation that caused the problem. But what is the best way to deliver that gene? 

The BGTC’s is focusing on using an adeno-associated virus (AAV) as a delivery vehicle. This approach has already proven effective in Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), and spinal muscular atrophy. The consortium will test several different approaches using AAV gene therapies starting with basic research and supporting those all the way to clinical trials. The knowledge gained from this collaborative approach, including developing ways to manufacture these AAVs and creating a standard regulatory approach, will help build a template that can then be used for other rare diseases to copy.

As part of the consortium CIRM will identify specific rare disease gene therapy research programs in California that are eligible to be part of the AMP BGTC. CIRM funding can then support the IND-enabling research, manufacturing and clinical trial activities of these programs.

“This knowledge network/consortium model fits in perfectly with our mission of accelerating transformative regenerative medicine treatments to a diverse California and world,” says Dr. Millan. “It is impossible for small, often isolated, groups of patients around the world to fund research that will help them. But pooling our resources, our skills and knowledge with the consortium means the work we support here may ultimately benefit people everywhere.”

Stem cells help researchers map out glaucoma in search for new treatments

Glaucoma is the world’s leading cause of irreversible blindness. There is no cure and current treatments are only able to slow down the progression of the disease. Now research using stem cells to create a genetic blueprint of glaucoma is giving scientist a powerful new tool to combat the disease.

Glaucoma occurs when healthy retinal ganglion cells, which relay information from the eyes to the brain, are damaged and die. However, researchers were unable to really understand what was happening because the only way to look at retinal ganglion cells was through very invasive procedures.

So, researchers in Australia took skin cells from people with glaucoma and people with healthy eyes and, using the iPSC method, turned them into retinal ganglion cells. They were then able to map the genetic expression of these cells and compare the healthy cells with the diseased ones.

In an interview with Science Daily, Professor Joseph Powell , who led the team, says they were able to identify more than 300 unique genetic features which could provide clues as to what is causing the vision loss.

“The sequencing identifies which genes are turned on in a cell, their level of activation and where they are turned on and off like a road network with traffic lights. This research gives us a genetic roadmap of glaucoma and identifies 312 sites in the genome where these lights are blinking. Understanding which of these traffic lights should be turned off or on will be the next step in developing new therapies to prevent glaucoma.”

Powell says by identifying underlying causes for glaucoma researchers may be able to develop new, more effective therapies.

The study is published in Cell Genomics.

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

The bootcamp helping in the fight against rare diseases

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Dr. Emil Kakkis at the Rare Entrepreneur Bootcamp

Imagine you or someone you love is diagnosed with a rare disease and then told, “There is no cure, there are no treatments and because it’s so rare no one is even doing any research into developing a treatment.” Sadly for millions of people that’s an all-too-common occurrence.

There are around 7,000 rare diseases affecting some 25-30 million Americans. Some of these are ultra-rare conditions where worldwide there may be only a few hundred people, or even a few dozen, diagnosed with it. And of all these rare diseases, only 5% have an approved therapy.

For the people struggling with a rare disease, finding a sense of hope in the face of all this can be challenging. Some say it feels as if they have been abandoned by the health care system. Others fight back, working to raise both awareness about the disease and funds to help support research to develop a treatment. But doing that without experience in the world of fund raising and drug development can pose a whole new series of challenges.

That’s where Ultragenyx comes into the picture. The company has a simple commitment to patients. “We aim to develop safe and effective treatments for many serious rare diseases as fast as we can, and we are committed to helping the whole rare disease community move forward by sharing our science and expertise to advance future development, whether by us or others.”

They live up to that commitment by hosting a Rare Entrepreneur Bootcamp. Every year they bring together a dozen or so patient or family organizations that are actively raising funds for a potential treatment approach and give them a 3-day crash course in what they’ll need to know to have a chance to succeed in rare disease drug development.

A panel discussion at the Rare Entrepreneur Bootcamp

Dr. Emil Kakkis, the founder of Ultragenyx, calls these advocates “warriors” because of all the battles they are going to face. He told them, “Get used to hearing no, because you are going to hear that a lot. But keep fighting because that’s the only way you get to ‘yes’.”

The bootcamp brings in experts to coach and advise the advocates on everything from presentation skills when pitching a potential investor, to how to collaborate with academic researchers, how to design a clinical trial, what they need to understand about manufacturing or intellectual property rights.

In a blog about the event, Arjun Natesan, vice president of Translational Research at Ultragenyx, wrote, “We are in a position to share what we’ve learned from bringing multiple drugs to market – and making the process easier for these organizations aligns with our goal of treating as many rare disease patients as possible. Our aim is to empower these organizations with guidance and tools and help facilitate their development of life-changing rare disease treatments.”

For the advocates it’s not just a chance to gain an understanding of the obstacles ahead and how to overcome them, it’s also a chance to create a sense of community. Meeting others who are fighting the same fight helps them realize they are not alone, that they are part of a bigger, albeit often invisible, community, working tirelessly to save the lives of their children or loved ones.  

CIRM also has a commitment to supporting the search for treatments for rare diseases. We are funding more than two dozen clinical trials, in addition to many earlier stage research projects, targeting rare conditions.

Stem cell agency invests in therapy using killer cells to target colorectal, breast and ovarian cancers

While there have been some encouraging advances in treating cancer in recent decades, there are still many cancers that either resist treatment or recur after treatment. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing in a therapy targeting some of these hard-to-treat tumors.

BioEclipse Therapeutics Inc. was awarded nearly $8M to test a therapy using immune cells loaded with a cancer-killing virus that targets cancer tissue but spares healthy tissue.

This is the 78th clinical trial funded directly by the Stem Cell Agency.

BioEclipse combines two approaches—an immune cell called a cytokine-induced killer (CIK) cell and a virus engineered to kill cancer cells called an oncolytic virus (OV)—to create what they call “a multi-mechanistic, targeted treatment.”

They will use the patient’s own immune cells and, in the lab, combine them with the OV. The cell/virus combination will then be administered back to the patient. The job of the CIK cells is to carry the virus to the tumors. The virus is designed to specifically attack and kill tumors and stimulate the patient’s immune system to attack the tumor cells. The goal is to eradicate the primary tumor and prevent relapse and recurrence.

“With the intent to develop this treatment for chemotherapy-resistant or refractory solid tumors—including colorectal cancer, triple negative breast cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma, and osteosarcoma—it addresses a significant unmet medical need in fatal conditions for which there are limited treatment options,” says Dr. Maria T. Millan, President and CEO of CIRM.  

The CIRM Board also approved more than $18 million in funding four projects under the Translation Projects program. The goal of this program is to support promising regenerative medicine (stem cell-based or gene therapy) projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use.

The awards went to:

ApplicationTitleInstitutionAward Amount
TRAN1-133442Optogenetic therapy for treating retinitis pigmentosa and
other inherited retinal diseases  
  Paul Bresge Ray Therapeutics Inc.  $3,999,553  
TRAN3-13332Living Synthetic Vascular Grafts with Renewable Endothelium    Aijun Wang UC Davis  $3,112,567    
TRAN1-13370Next generation affinity-tuned CAR for prostate cancer    Preet Chaudhary University of Southern California  $5,805,144  
TRAN1-3345Autologous MPO Knock-Out Hematopoietic Stem and
Progenitor Cells for Pulmonary Arterial Hypertension  
  Don Kohn UC Los Angeles  $5,207,434  

Promoting stem cell therapies, racial justice and fish breeding

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Jan Nolta, PhD, in her lab at UC Davis; Photo courtesy UC Davis

Working at CIRM you get to meet many remarkable people and Dr. Jan Nolta certainly falls into that category. Jan is the Director of the Stem Cell Program at UC Davis School of Medicine. She also directs the Institute for Regenerative Cures and is scientific director of both the Good Manufacturing Practice clean room facility at UC Davis and the California Umbilical Cord Blood Collection Program.

As if that wasn’t enough Jan is part of the team helping guide UC Davis’ efforts to expand its commitment to diversity, equity and inclusion using a variety of methods including telemedicine, to reach out into rural and remote communities.

She is on the Board of several enterprises, is the editor of the journal Stem Cells and, in her copious spare time, has dozens of aquariums and is helping save endangered species.

So, it’s no wonder we wanted to chat to her about her work and find out what makes her tick. Oh, and what rock bands she really likes. You might be surprised!

That’s why Jan is the guest on the latest edition of our podcast ‘Talking ‘Bout (re)Generation’.

I hope you enjoy it.

Stem Cell Agency Board Approves Funding for Rare Immune Disorder

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Taylor Lookofsky (center), a person with IPEX syndrome, with his father Brian and Dr. Rosa Bacchetta

IPEX syndrome is a rare condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. The syndrome mostly affects boys, is diagnosed in the first year of life and is often fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) invested almost $12 million in a therapy being tested in a clinical trial to help these patients.

Children born with IPEX syndrome have abnormalities in the FOXP3 gene. This gene controls the production of a type of immune cell called a T Regulatory or Treg cell. Without a normal FOXP3 +Treg cells other immune cells attack the body leading to the development of IPEX syndrome, Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive.

Current treatments involve the use of steroids to suppress the immune system – which helps ease symptoms but doesn’t slow down the progression of the disease – or a bone marrow stem cell transplant.  However, a transplant requires a healthy, closely matched donor to reduce the risk of a potentially fatal transplant complication called graft vs host disease, in which the donated immune cells attack the recipient’s tissues.

Dr. Rosa Bacchetta and her team at Stanford University have developed a therapy using the patient’s own natural CD4 T cells that, in the lab, have been genetically modified to express the FoxP3 gene and converted into Treg cells. Those cells are then re-infused into the patient with a goal of determining if this approach is both safe and beneficial. Because the cells come from the patients there will be fewer concerns about the need for immunosuppressive treatment to stop the body rejecting the cells. It will also help avoid the problems of finding a healthy donor and graft vs host disease.

Dr. Bacchetta has received approval from the Food and Drug Administration (FDA) to test this approach in a Phase 1 clinical trial for patients suffering with IPEX syndrome.

“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,” says Dr. Maria T. Millan, the President and CEO of CIRM. “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 resulting from dysfunctional regulatory T cells.”

In addition to a strong scientific recommendation to fund the project the review team also praised it for the applicants’ commitment to the principles of Diversity, Equity and Inclusion in their proposal. The project proposes a wide catchment area, with a strong focus on enrolling people who are low-income, uninsured or members of traditionally overlooked racial and ethnic minority communities.