Positive results from CIRM-funded LAD-I trial presented at the 62nd American Society of Hematology Annual Meeting

Gaurav Shah, M.D., CEO and President of Rocket Pharmaceuticals

Leukocyte Adhesion Deficiency-I (LAD-I) is a rare pediatric disease caused by a mutation in a specific gene that causes low levels of a protein called CD18. Due to low levels of CD18, the adhesion of immune cells is affected, which negatively impacts the body’s ability to combat infections.

Rocket Pharmaceuticals is conducting a CIRM-funded ($6.56 M) clinical trial that is testing a treatment that uses a gene therapy called RP-L201. The therapy uses a patient’s own blood stem cells and inserts a functional version of the gene.  These modified stem cells are then reintroduced back into the patient. The goal is to establish functional immune cells, enabling the body to combat infections. Previous studies have indicated that an increase in CD18 to 4-10% is associated with survival into adulthood. 

The company presented interim data from the trial at the 62nd American Society of Hematology (ASH) Annual Meeting in the form of an oral presentation. The data presented is from three pediatric patients with severe LAD-I, which is defined by CD18 expression of less than 2%. The patients were all treated with RP-L201. Patient One was 9-years of age at enrollment and had been followed for 12-months as of a cutoff date of November 2020. Patient Two was 3-years of age at enrollment and had been followed for over 6-months. Patient Three was 7-months of age at enrollment and was recently treated with RP-L201.

Key highlights from the presentation include:

  • RP-L201 was well tolerated, no safety issues reported with infusion or post-treatment
  • All patients achieved hematopoietic (blood) reconstitution within 5-weeks
    • 12 months post-treatment, Patient One demonstrated durable CD18 expression of approximately 40%,
    • 6-months post-treatment, Patient Two demonstrated CD18 expression of 23%
    • 2-months post-treatment, Patient Three demonstrated CD18 expression of 76%

In a press release from Rocket, Gaurav Shah, M.D., CEO and President of Rocket, expressed excitement about these results.

“…we continue to see encouraging evidence of efficacy for RP-L201 for the treatment of LAD-I. Patients have shown sustained CD18 expression of 23% to 40%, far exceeding the 4-10% threshold associated with survival into adulthood…”

To view the presentations at the conclusion of the oral presentation, click the link here.

CIRM funded trial for sickle cell disease gives patient a chance for a better future

Evie Junior is participating in a CIRM funded clinical trial for sickle cell disease that uses a stem cell gene therapy approach. Image credit: UCLA Broad Stem Cell Research Center

For Evie Junior, personal health and fitness have always been a top priority. During his childhood, he was active and played football, basketball, and baseball in the Bronx, New York. One would never guess that after playing these sports, some nights he experienced pain crises so severe that he was unable to walk. One would also be shocked to hear that he had to have his gallbladder and spleen removed as a child as well.

The health issues that Evie has faced all of his life are related to his diagnosis of sickle cell disease (SCD), a genetic, blood related disorder. SCD causes blood stem cells in the bone marrow, which make blood cells, to produce hard, “sickle” shaped red blood cells. These “sickle” shaped blood cells die early, causing there to be a lack of red blood cells to carry oxygen throughout the body. Due to their “sickle” shape, these cells also get stuck in blood vessels and block blood flow, resulting in excruciating bouts of pain that come on with no warning and can leave patients hospitalized for days.

SCD affects 100,000 people in the United States, the majority of whom are from the Black and Latinx communities, and millions more people around the world,. It can ultimately lead to strokes, organ damage, and early death.

Growing up with SCD inspired Evie to become an emergency medical technician, where he would be able to help patients treat their pain en route to the hospital, in much the same way he has managed his own pain crises for his whole life. Unfortunately as time passed, Evie’s pain crises became harder and harder to manage.

Then in July 2019, Evie decided to enroll in a CIRM funded clinical trial for a stem cell gene therapy to treat SCD. The therapy, developed by Dr. Don Kohn at UCLA, is intended to correct the genetic mutation in a patient’s blood stem cells to allow them to produce healthy red blood cells. Dr. Kohn has already applied the same concept to successfully treat several genetic immune system deficiencies in two other CIRM funded trials, including a cure for a form of Severe Combined Immunodeficiency, also known as bubble baby disease, as well as X-Linked Chronic Granulomatous Disease.

After some delays related to the coronavirus pandemic, Evie finally received an infusion of his own blood stem cells that had been genetically modified to overcome the mutation that causes SCD in July 2020.

Although the results are still very preliminary, so far they look very promising. Three months after his treatment, blood tests indicated that 70% of Evie’s blood stem cells had the new corrected gene. The UCLA team estimates that a 20% correction would be enough to prevent future sickle cell complications. What is also encouraging is that Evie hasn’t had a pain crisis since undergoing the treatment.

In a press release from UCLA, Dr. Kohn discusses that he is cautiously optimistic about these results.

“It’s too early to declare victory, but it’s looking quite promising at this point. Once we’re at six months to a year, if it looks like it does now, I’ll feel very comfortable that he’s likely to have a permanent benefit.”

In the same press release, Evie talks about what a cure would mean for his future and his life going forward.

“I want to be present in my kids’ lives, so I’ve always said I’m not going to have kids unless I can get this cured. But if this works, it means I could start a family one day.”

You can learn more about Evie’s story and the remarkable CIRM funded work at UCLA by watching the video below.

CIRM Board Approves Four New Clinical Trials

A breakdown of CIRM’s clinical trials by disease area

This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved four new clinical trials in addition to ten new discovery research awards.

These new awards bring the total number of CIRM-funded clinical trials to 68.  Additionally, these new additions have allowed the state agency to exceed the goal of commencing 50 new trials outlined in its five year strategic plan.

$8,970,732 was awarded to Dr. Steven Deeks at the University of California San Francisco (UCSF) to conduct a clinical trial that modifies a patient’s own immune cells in order to treat and potentially cure HIV. 

Current treatment of HIV involves the use of long-term antiretroviral therapy (ART).  However, many people are not able to access and adhere to long-term ART.

Dr. Deeks and his team will take a patient’s blood and extract T cells, a type of immune cell.  The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells.  The modified T cells are then reintroduced back into the patient.

The goal of this one time therapy is to act as a long-term control of HIV with patients no longer needing to take ART, in effect a form of HIV cure.  This approach would also address the needs of those who are not able to respond to current approaches, which is estimated to be 50% of those affected by HIV globally. 

$3,728,485 was awarded to Dr. Gayatri Rao from Rocket Pharmaceuticals to conduct a clinical trial using a gene therapy for infantile malignant osteopetrosis (IMO), a rare and life-threatening disorder that develops in infancy.  IMO is caused by defective bone cell function, which results in blindness, deafness, bone marrow failure, and death very early in life. 

The trial will use a gene therapy that targets IMO caused by mutations in the TCIRG1 gene.  The team will take a young child’s own blood stem cells and inserting a functional version of the TCIRG1 gene.  The newly corrected blood stem cells are then introduced back into the child, with the hope of halting or preventing the progression of IMO in young children before much damage can occur. 

Rocket Pharmaceuticals has used the same gene therapy approach for modifying blood stem cells in a separate CIRM funded trial for a rare pediatric disease, which has shown promising results.

$8,996,474 was awarded to Dr. Diana Farmer at UC Davis to conduct a clinical trial of in utero repair of myelomeningocele (MMC), the most severe form of spina bifida.  MMC is a birth defect that occurs due to incomplete closure of the developing spinal cord, resulting in neurological damage to the exposed cord.  This damage leads to lifelong lower body paralysis, and bladder and bowel dysfunction.

Dr. Farmer and her team will use placenta tissue to generate mesenchymal stem cells (MSCs).  The newly generated MSCs will be seeded onto an FDA approved dural graft and the product will be applied to the spinal cord while the infant is still developing in the womb.  The goal of this therapy is to help promote proper spinal cord formation and improve motor function, bladder function, and bowel function. 

The clinical trial builds upon the work of CIRM funded preclinical research.

$8,333,581 was awarded to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease (SCD).  This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s  “Cure Sickle Cell” Initiative.  The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.

SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape.  Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death. 

The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression.  The modified blood stem cells will then be reintroduced back into the patient.  The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease.

“Today is a momentus occasion as CIRM reaches 51 new clinical trials, surpassing one of the goals outlined in its five year strategic plan,” says Maria T. Millan, M.D., President and CEO of CIRM.  “These four new trials, which implement innovative approaches in the field of regenerative medicine, reflect CIRM’s ever expanding and diverse clinical portfolio.”

The Board also approved ten awards that are part of CIRM’s Quest Awards Prgoram (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.

The awards are summarized in the table below:

  APPLICATION  TITLE  INSTITUTION  AWARD AMOUNT  
    DISC2-12169  Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.  UCLA  $250,000
  DISC2-12170Development of COVID-19 Antiviral Therapy Using Human iPSC-Derived Lung Organoids  UC San Diego  $250,000
  DISC2-12111Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia  UCLA  $250,000
  DISC2-12158Development of a SYF2 antisense oligonucleotide (ASO) treatment for ALSUniversity of Southern California  $249,997
    DISC2-12124Dual angiogenic and immunomodulating nanotechnology for subcutaneous stem cell derived islet transplantation for the treatment of diabetes  Lundquist Institute  $250,000
  DISC2-12105Human iPSC-derived chimeric antigen receptor-expressing macrophages for cancer treatment  UC San Diego  $250,000
  DISC2-12164Optimization of a human interneuron cell therapy for traumatic brain injury  UC Irvine  $250,000
  DISC2-12172Combating COVID-19 using human PSC-derived NK cells  City of Hope  $249,998
  DISC2-12126The First Orally Delivered Cell Therapy for the Treatment of Inflammatory Bowel Disease  Vitabolus Inc.  $249,000
    DISC2-12130Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)  UC Irvine  $249,968

CIRM-funded treatment gets orphan drug and rare pediatric disease designations from FDA

From left to right: Brian Lookofsky , Taylor Lookofsky, and Rosa Bacchetta, M.D.
Picture taken October 2019

Last year, CIRM awarded $5.53 million to Rosa Bacchetta, M.D. at Stanford University to complete the work necessary to conduct a clinical trial for IPEX syndrome. This is a rare disease caused by mutations in the FOXP3 gene, which leaves people with the condition vulnerable to immune system attacks on their organs and tissues. These attacks can be devastating, even fatal.

Flash forward to the present day and the CIRM-funded treatment that Dr. Bacchetta has been working on has received both an orphan drug and a rare pediatric disease designation from the Food and Drug Administration (FDA).

Orphan drug designation is a special status given by the Food and Drug Administration (FDA) for potential treatments of rare diseases that affect fewer than 200,000 in the U.S. This type of status can significantly help advance treatments for rare diseases by providing financial incentives in the form of tax credits towards the cost of clinical trials and prescription drug user fee waivers.

Under the FDA’s rare pediatric disease designation program, the FDA may grant priority review to Dr. Bacchetta if this treatment eventually receives FDA approval. The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and affects fewer than 200,000 people in the U.S.

“The designations granted by the FDA are a strong encouragement for our team to meet the goal of submitting the IND in 2021 and start the clinical trial for IPEX patients who are so much looking forward to new therapeutic options.” said Dr. Bacchetta.

But this begs the question, what exactly is IPEX syndrome? What is the approach that Dr. Bacchetta is working on? For those of you interested in the deeper scientific dive, we will elaborate on this complex disease and promising approach.

IPEX syndrome is a rare disease that primarily affects males and is caused by a genetic mutation that leads to lack of function of specialized immune cells called regulatory T cells (Tregs).

Without functional Tregs, a patient’s own immune cells attack the body’s own tissues and organs, a phenomenon known as autoimmunity.  This affects many different areas such as the intestines, skin, and hormone-producing glands and can be fatal in early childhood. 

Current treatment options include a bone marrow transplant and immune suppressing drugs.  However, immune suppression is only partially effective and can cause severe side effects while bone marrow transplants are limited due to lack of matching donors.

Dr. Rosa Bacchetta and her team at Stanford will take a patient’s own blood in order to obtain CD4+ T cells.  Then, using gene therapy, they will insert a normal version of the mutated gene into the CD4+ T cells, allowing them to function like normal Treg cells.  These Treg-like cells would then be reintroduced back into the patient, hopefully creating an IPEX-free blood supply and resolving the autoimmunity.

Furthermore, if successful, this treatment could be adapted for treatment of other, more common, autoimmune conditions where Treg cells are the underlying problem.

The same day that CIRM approved funding for this approach, Taylor Lookofsky, a young man with IPEX syndrome, talked about the impact the condition has had on his life.

It’s a powerful reminder that syndromes like this, because they affect a small number of people, are often overlooked and have few resources devoted to finding new treatments and cures. After hearing Taylor’s story, you come to appreciate his courage and determination, and why the funding CIRM provides is so important in helping researchers like Dr. Bacchetta find therapies to help people like Taylor.

The full transcript of his talk can be accessed on a previous blog post.

A look back at 15 years of CIRM funding at UCLA

Researchers in the lab of CIRM grantee Donald Kohn, M.D.
Image Credit: UCLA Broad Stem Cell Center

Since the first grant was issued in April 2006, CIRM has funded a wide range of research conducted by top scientists at UCLA for a wide range of diseases. To give a retrospective look at all the research, UCLA released a news article that describes all this work up until this past September. During this period, UCLA researchers were awarded 120 grants totaling more than $307 million. We’ll highlight some of these findings from the article below.

51 Basic Biology CIRM Grants

Basic biology research encompasses very early stage work that focuses on the very essentials such as how stem cells work, how to successfully turn a stem cell into another type of cell, and other basic mechanisms that underly the stem cell research field. This research is critical because they inform future therapies for dozens of conditions including heart disease, genetic and blood disorders, cancer, spinal cord injuries and neurological disorders.

3 Consecutive Year-Long CIRM Training Grants

These CIRM grants are essential in training the next generation of scientists and physicians in the regenerative medicine field. The CIRM training grants supported 146 graduate students, post‐doctoral fellows, and clinical fellows working in UCLA laboratories by providing them year-long  training fellowships. This program was so successful that the UCLA Broad Stem Cell Research Center funded 26 additional fellowships to supplement CIRM’s support.

5 COVID-19 Related Grants

Shortly after the coronavirus pandemic, CIRM authorized  $5 million in emergency funding to fund COVID-19 related projects. UCLA has received a $1.02 million to support four discovery research projects and one translational project. Discovery research promotes promising new technologies that could be translated to enable broad use and improve patient care. Translational research takes it a step further by promoting the activities necessary for advancement to clinical study of a potential therapy.

1 Alpha Stem Cell Clinic (ASCC) Grant

One award was used to establish the UCLA‐UCI Alpha Stem Cell Clinic. It is one of five leading medical centers throughout California that make up the CIRM ASSC Network, which specializes in the delivery of stem cell therapies by providing world-class, state of the art infrastructure to support clinical research.

8 Clinical Trials

Out of the 64 CIRM-funded clinical trials to date, eight of these have been conducted at UCLA. Most notably, this includes a stem cell gene therapy approach developed by Donald Kohn, M.D. The approach was used in three different clinical trials for the following genetic diseases: X-linked chronic granulomatous disease (X-CGD), bubbly baby disease (also known as SCID), and sickle cell disease. The SCID trial resulted in over 50 infants being cured of the disease, including little Evie. The other five clinical trials conducted at UCLA were for corneal damage, lung damage, skin cancer, sarcomas, and solid tumors.

Wide Reach of Conditions

CIRM grants at UCLA have supported research related to many conditions, including the following:

To read the full UCLA article that discusses some of the other grants, click here.

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 Bridges program prepared student for research of a rare disease

Ian Blong, Ph.D., CIRM San Francisco State University Bridges to Stem Cell Research Alumnus

Recently, The New York Times released a powerful article that tells the stories of four different families navigating the challenges of having a family member with a rare disease. One of these stories focused on Matt Wilsey, a tech entrepreneur and investor in California’s Silicon Valley, and his daughter Grace, who was born with an extremely rare genetic disorder named NGLY1 deficiency. This genetic disorder causes developmental delay, intellectual disability, seizures, and other movement issues.

Matt and Kristen Wilsey with their 10-year-old daughter Grace, who has a rare genetic disorder, at the Grace Science headquarters in Menlo Park, Calif.
Image Credit: James Tensuan for The New York Times

Matt decided to put his entrepreneurial and networking skills to good use in order to form Grace Science Foundation, an organization whose focus is to pioneer approaches to scientific discovery in order to develop a cure for NGLY1 deficiency. One researcher that Matt brought on board was Carolyn Bertozzi, Ph.D., a chemist from Stanford University. A graduate student in her laboratory, Ian Blong, Ph.D., decided to study NGLY1 and was able to complete his dissertation while working on this topic at Stanford University.

Ian’s journey towards obtaining his Ph.D. started after being accepted into the San Francisco State University (SFSU) CIRM Bridges to Stem Cell Research Master’s Program. CIRM funding for this program allowed students like Ian to take courses at SFSU while also working in labs at world renown institutions in the Bay Area such as UCSF, Stanford, and UC Berkeley.

Carolyn Bertozzi, Ph.D.
Image Credit: L.A. Cicero

In exploring the various options afforded to him by the CIRM, Ian found Dr. Bertozzi’s lab at UC Berkeley, where he focused on early stage discovery research. His master’s thesis project focused on how to generate rare neuronal and and neural crest cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Both of these stem cell types can generate virtually any kind of cell, but iPSCs are unique in that they can be generated from the adult cells (such as skin) of a patient.

Ian decided to continue his studies in Dr. Bertozzi’s lab by continuing his research in a Ph.D. program at UC Berkeley. He credits the SFSU CIRM Bridges Program with giving him the opportunity to work under a prestigious PI and in her lab at UC Berkeley, which allowed him to continue his studies there.

“The CIRM Bridges Program gave me the confidence and resources to pursue my dreams. Being able to have the capability of going to Berkeley and do research with top tier scientists along with the support from CIRM. Without CIRM, I wouldn’t have had the courage to go to those universities to get my foot in the door.”

Eventually, Dr. Bertozzi move her operations to Stanford University and Ian continued his Ph.D. studies there. Stanford provided him the opportunity to focus more on the translational stage, which is an area of research aimed at developing a therapeutic candidate. Going into his Ph.D. work, Ian was able to build upon his previous “discovery stage” knowledge of generating neuronal and neural crest cells from iPSCS and hESCs.

An area of his work at Stanford focused on generating neural crest cells from iPSCs of those with NGLY1 deficiency. The goal was to identify a phenotype, which is an observable characteristic such as physical form. Identifying this would help better understand potential differentiation pathways that underlie NGLY1 deficiency, which could lead to the development a potential treatment for the condition.

Flash forward to present day and Ian is still using the knowledge he learned from his time in the SFSU CIRM Bridges to Stem Cell Research Program. He is currently a scientist at the healthcare company Roche, where his focus is on manufacturing future diagnostics and therapeutics on a much larger scale, a complex and extremely critical process necessary in widely distributing potential stem cell-based treatments.

Ian’s experience and opportunities provided to him is just one of the many examples of how the various CIRM Bridges Programs across California have given students the resources needed to become the next generation of scientists.

It’s all about the patients

Ronnie, born with a fatal immune disorder now leading a normal life thanks to a CIRM-funded stem cell/gene therapy: Photo courtesy of his mum Upasana

Whenever you are designing something new you always have to keep in mind who the end user is. You can make something that works perfectly fine for you, but if it doesn’t work for the end user, the people who are going to work with it day in and day out, you have been wasting your time. And their time too.

At CIRM our end users are the patients. Everything we do is about them. Starting with our mission statement: to accelerate stem cell treatments to patients with unmet medical needs. Everything we do, every decision we make, has to keep the needs of the patient in mind.

So, when we were planning our recent 2020 Grantee Meeting (with our great friends and co-hosts UC Irvine and UC San Diego) one of the things we wanted to make sure didn’t get lost in the mix was the face and the voice of the patients. Often big conferences like this are heavy on science with presentations from some of the leading researchers in the field. And we obviously wanted to make sure we had that element at the Grantee meeting. But we also wanted to make sure that the patient experience was front and center.

And we did just that. But more on that in a minute. First, let’s talk about why the voice of the patient is important.

Some years ago, Dr. David Higgins, a CIRM Board member and patient advocate for Parkinson’s Disease (PD), said that when researchers are talking about finding treatments for PD they often focus on the dyskinesia, the trembling and shaking and muscle problems. However, he said if you actually asked people with PD you’d find they were more concerned with other aspects of the disease, the insomnia, anxiety and depression among other things. The key is you have to ask.

Frances Saldana, a patient advocate for research into Huntington’s disease

So, we asked some of our patient advocates if they would be willing to be part of the Grantee Meeting. All of them, without hesitation, said yes. They included Frances Saldana, a mother who lost three of her children to Huntington’s disease; Kristin MacDonald, who lost her sight to a rare disorder but regained some vision thanks to a stem cell therapy and is hoping the same therapy will help restore some more; Pawash Priyank, whose son Ronnie was born with a fatal immune disorder but who, thanks to a stem cell/gene therapy treatment, is now healthy and leading a normal life.

Because of the pandemic everything was virtual, but it was no less compelling for that. We interviewed each of the patients or patient advocates beforehand and those videos kicked off each session. Hearing, and seeing, the patients and patient advocates tell their stories set the scene for what followed. It meant that the research the scientists talked about took on added significance. We now had faces and names to highlight the importance of the work the scientists were doing. We had human stories. And that gave a sense of urgency to the work the researchers were doing.

But that wasn’t all. After all the video presentations each session ended with a “live” panel discussion. And again, the patients and patient advocates were a key part of that. Because when scientists talk about taking their work into a clinical trial they need to know if the way they are setting up the trial is going to work for the patients they’re hoping to recruit. You can have the best scientists, the most promising therapy, but if you don’t design a clinical trial in a way that makes it easy for patients to be part of it you won’t be able to recruit or retain the people you need to test the therapy.

Patient voices count. Patient stories count.

But more than anything, hearing and seeing the people we are trying to help reminds us why we do this work. It’s so easy to get caught up in the day to day business of our jobs, struggling to get an experiment to work, racing to get a grant application in before the deadline. Sometimes we get so caught up in the minutiae of work we lose sight of why we are doing it. Or who we are doing it for.

At CIRM we have a saying; come to work every day as if lives depend on you, because lives depend on you. Listening to the voices of patients, seeing their faces, hearing their stories, reminds us not to waste a moment. Because lives depend on all of us.

Here’s one of the interviews that was featured at the event. I do apologize in advance for the interviewer, he’s rubbish at his job.

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

Graphite Bio launches and will prepare for clinical trial based on CIRM-funded research

Josh Lehrer, M.D., CEO of Graphite Bio

This week saw the launch of the 45th startup company enabled by CIRM funding of translational research at California academic institutions. Graphite Bio officially launched with the help of $45M in funding led by bay area venture firms Versant Ventures and Samsara BioCapital to spinout a novel CRISPR gene editing platform from Stanford University to treat severe diseases. Graphite Bio’s lead candidate is for sickle cell disease and it harnesses CRISPR gene correction technology to correct the single DNA mutation in sickle cell disease and to restore normal hemoglobin expression in the red blood cells of sickle cell patients (Learn more about CRISPR from a previous blog post linked here).

Matt Porteus, M.D., Ph.D (left) and Maria Grazia Roncarolo, M.D. (right)
Graphite Bio scientific founders

Matt Porteus, M.D., Ph.D and Maria Grazia Roncarolo, M.D., both from Stanford University, are the company’s scientific founders. Dr. Porteus, Dr. Roncarolo, and the Stanford team are currently supported by a CIRM  late stage preclinical grant  to complete the final preclinical studies and to file an Investigational New Drug application with the FDA, which will enable Graphite Bio to commence clinical studies of the CRISPR sickle cell disease gene therapy candidate in sickle cell patients in 2021.

Josh Lehrer, M.D., was appointed CEO of Graphite Bio and elaborated on the company’s gene editing approach in a news release.

“Our flexible, site-specific approach is extremely powerful and could be used to definitively correct the underlying causes of many severe genetic diseases, and also is applicable to broader disease areas. With backing from Versant and Samsara, we look forward to progressing our novel medicines into the clinic for patients with high unmet needs.”

In a press release, Dr. Porteus take a retrospective look on his preclinical research and its progress towards a clinical trial.

“It is gratifying to see our work on new gene editing approaches being translated into novel therapies. I’m very excited to be working with Versant again on a start-up and I look forward to collaborating with Samsara and the Graphite Bio team to bring a new generation of genetic treatments to patients.”

CIRM’s funding of late stage preclinical projects such this one is critical to its funding model, which de-risks the discovery, translational development and clinical proof of concept of innovative stem cell-based treatments until they can attract industry partnerships. You can learn more about CIRM-enabled spinout companies and CIRM’s broader effort to facilitate industry partnering for its portfolio projects on CIRM’s Industry Alliance Program website.

You can contact CIRM’s Director of Business Development at the email below to learn more about the Industry Alliance Program.

Shyam Patel, Ph.D.
Director, Business Development
Email: spatel@cirm.ca.gov