Update on SCID patient enrolled in CIRM-funded gene therapy trial

Photo credit: UCSF

Hataalii Tiisyatonii Begay (HT) is paving the road for newborns with SCID. When HT was born in 2018 in a remote part of the Navajo nation, he was quickly diagnosed with a rare and -usually fatal- condition. Today, thanks to a therapy developed at UCSF and funded by CIRM, he’s a healthy four-year-old boy running around in cowboy boots.

The California Institute for Regenerative Medicine (CIRM) has invested $12 million to test this therapy in a clinical trial at UC San Francisco.

The disorder is Artemis-SCID, a form of severe combined immunodeficiency disease. Children born with this condition have no functioning immune system so even a simple infection can prove life-threatening or fatal.

Currently, the only approved treatment for Artemis-SCID is a bone-marrow transplant, but many children are unable to find a healthy matched donor for that procedure. Even when they do find a donor, they often need regular injections of antibodies to boost their immune system.

Dr. Morton Cowen and Dr. Jennifer Puck. Photo credit: UCSF

In this clinical trial, UCSF doctors Morton Cowan and Jennifer Puck are using the patient’s own blood stem cells, taken from their bone marrow. In the lab, the cells are modified to correct the genetic mutation that causes Artemis-SCID and then re-infused back into the patients. The goal is that over the course of several months these cells will create a new blood supply, one that is free of Artemis-SCID, and that will in turn help repair the child’s immune system.

In April 2022, HT finally moved back home to Arizona. Nowadays, HT is off his medication and living the life of a normal and happy young child. On the Arizona ranch, there are horses to pet, cattle and sheep to tend, and streams to cool his hands in.

Watch the video below to find out more about HT’s journey and the team at UCSF behind the pioneering trial.

Video courtesy of UCSF

Making transplants easier for kids, and charting a new approach to fighting solid tumors.

Every year California performs around 100 kidney transplants in children but, on average, around 50 of these patients will have their body reject the transplant. These children then have to undergo regular dialysis while waiting for a new organ. Even the successful transplants require a lifetime of immunosuppression medications. These medications can prevent rejection but they also increase the risk of infection, gastrointestinal disease, pancreatitis and cancer.

Dr. Alice Bertaina and her team at Stanford University were awarded $11,998,188 to test an approach that uses combined blood stem cell (HSC) and kidney transplantation with the goal to improve outcomes with kidney transplantation in children. This approach seeks to improve on the blood stem cell preparation through an immune-based purification process.

In this approach, the donor HSC are transplanted into the patient in order to prepare for the acceptance of the donor kidney once transplanted. Donor HSC give rise to cells and conditions that re-train the immune system to accept the kidney. This creates a “tolerance” to the transplanted kidney providing the opportunity to avoid long-term need for medications that suppress the immune system.

Pre-clinical data support the idea that this approach could enable the patient to stop taking any immunosuppression medications within 90 days of the surgery.

Dr. Maria T. Millan, President and CEO of CIRM, a former pediatric transplant surgeon and tolerance researcher states that “developing a way to ensure long-term success of organ transplantation by averting immune rejection while avoiding the side-effects of life-long immunosuppression medications would greatly benefit these children.”

The CIRM Board also awarded $7,141,843 to Dr. Ivan King and Tachyon Therapeutics, Inc to test a drug showing promise in blocking the proliferation of cancer stem cells in solid tumors such as colorectal and gastrointestinal cancer.

Patients with late-stage colorectal cancer are typically given chemotherapy to help stop or slow down the progression of the disease. However, even with this intervention survival rates are low, usually not more than two years.

Tachyon’s medication, called TACH101, is intended to target colorectal cancer (CRC) stem cells as well as the bulk tumor by blocking an enzyme called KDM4, which cancer stem cells need to grow and proliferate.

In the first phase of this trial Dr. King and his team will recruit patients with advanced or metastatic solid tumors to assess the safety of TACH101, and determine what is the safest maximum dose. In the second phase of the trial, patients with gastrointestinal tumors and colorectal cancer will be treated using the dose determined in the first phase, to determine how well the tumors respond to treatment.  

The CIRM Board also awarded $5,999,919 to Dr. Natalia Gomez-Ospina and her team at Stanford University for a late-stage preclinical program targeting Severe Mucopolysaccharidosis type 1, also known as Hurler syndrome. This is an inherited condition caused by a faulty gene. Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs. There is no effective treatment and life expectancy for many of these children is only around ten years.

Dr. Gomez-Ospina will use the patient’s own blood stem cells that have been genetically edited to restore the missing enzyme. The goal of this preclinical program is to show the team can manufacture the needed cells, to complete safety studies and to apply to the US Food and Drug Administration for an Investigational New Drug (IND), the authorization needed to begin a clinical trial in people.

Finally the Board awarded $20,401,260 to five programs as part of its Translational program. The goal of the Translational program is to support promising stem cell-based or gene projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use. Those can include therapeutic candidates, diagnostic methods  or devices and novel tools that address critical bottlenecks in research.

The successful applicants are:

APPLICATIONTITLEPRINCIPAL INVESTIGATOR – INSTITUTIONAMOUNT  
TRAN4-14124Cell Villages and Clinical Trial in a Dish with Pooled iPSC-CMs for Drug DiscoveryNikesh Kotecha — Greenstone Biosciences  $1,350,000
TRAN1-14003Specific Targeting Hypoxia Metastatic Breast Tumor with Allogeneic Off-the-Shelf Anti-EGFR CAR NK Cells Expressing an ODD domain of HIF-1αJianhua Yu — Beckman Research Institute of City of Hope  $6,036,002  
TRAN1-13983CRISPR/Cas9-mediated gene editing of Hematopoietic
stem and progenitor cells for Friedreich’s ataxia
Stephanie Cherqui — University of California, San Diego  $4,846,579
TRAN1-13997Development of a Gene Therapy for the Treatment of
Pitt Hopkins Syndrome (PHS) – Translating from Animal Proof of Concept to Support Pre-IND Meeting
Allyson Berent — Mahzi Therapeutics  $4,000,000
TRAN1-13996Overcoming resistance to standard CD19-targeted CAR
T using a novel triple antigen targeted vector
William J Murphy — University of California, Davis  $4,168,679

Sweet 16 and counting for stem cell clinical trial

Dr. Judy Shizuru: Photo courtesy Jasper Therapeutics

Over the years the California Institute for Regenerative Medicine (CIRM) has invested a lot in helping children born with severe combined immunodeficiency (SCID), a fatal immune disorder. And we have seen great results with some researchers reporting a 95 percent success rate in curing these children.

Now there’s more encouraging news from a CIRM-funded clinical trial with Jasper Therapeutics. They have announced that they have tested their approach in 16 patients, with encouraging results and no serious adverse events.

Let’s back up a little. Children born with SCID have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life. Several of the approaches CIRM has funded use the child’s own blood stem cells to help fix the problem. But at Jasper Therapeutics they are using another approach. They use a bone marrow or hematopoietic stem cell transplant (HCT).   This replaces the child’s own blood supply with one that is free of the SCID mutation, which helps restore their immune system.

However, there’s a problem. Most bone marrow transplants use chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. It can be effective, but it is also toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

To get around that problem Jasper Therapeutics is using an antibody called JSP191 – developed with CIRM funding – that directs the patient’s own immune cells to kill diseased blood stem cells, creating room to transplant new, healthy cells. To date the therapy has already been tested in 16 SCID patients.

In addition to treating 16 patients treated without any apparent problems,  Jasper has also been granted Fast Track Designation by the US Food and Drug Administration. This can help speed up the review of treatments that target serious unmet conditions. They’ve also been granted both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.

In a news release, Ronald Martell, President and CEO of Jasper Therapeutics said:

“The FDA’s Fast Track designation granted for JSP191 in Severe Combined Immunodeficiency (SCID) reinforces the large unmet medical need for patients with this serious disease. Along with its previous designations of Orphan and Rare Pediatric Disease for JSP191, the FDA’s Fast Track recognizes JSP191’s potential role in improving clinical outcomes for SCID patients, many of whom are too fragile to tolerate the toxic chemotherapy doses typically used in a transplant.”

Fast Track Designation for a therapy making transplants safer for children with a fatal immune disorder

Bone marrow transplant

For children born with severe combined immunodeficiency (SCID) life can be very challenging. SCID means they have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life.

There are stem cell/gene therapies funded by the California Institute for Regenerative Medicine (CIRM), such as ones at UCLA and UCSF/St. Judes, but an alternative method of treating, and even curing the condition, is a bone marrow or hematopoietic stem cell transplant (HCT). This replaces the child’s blood supply with one that is free of the SCID mutation, which helps restore their immune system.

However, current HCT 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.

To change that, Dr. Judy Shizuru at Stanford University, with CIRM funding, developed an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells, creating the room needed to transplant new, healthy cells. The goal was to make stem cell transplants safer and more effective for the treatment of many life-threatening blood disorders.

That approach, JSP191, is now being championed by Jasper Therapeutics and they just got some very good news from the Food and Drug Administration (FDA). The FDA has granted JSP191 Fast Track Designation, which can speed up the review of therapies designed to treat serious conditions and fill unmet medical needs.

In a news release, Ronald Martell, President and CEO of Jasper Therapeutics, said this is good news for the company and patients: “This new Fast Track designation recognizes the potential role of JSP191 in improving clinical outcomes for these patients and will allow us to more closely work with the FDA in the upcoming months to determine a path toward a Biologics License Application (BLA) submission.”

Getting a BLA means Jasper will be able to market the antibody in the US and make it available to all those who need it.

This is the third boost from the FDA for Jasper. Previously the agency granted JSP191 both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.

A better, faster, more effective way to edit genes

Clinical fellow Brian Shy talks with postdoctoral scholar Tori Yamamoto in the Marson Lab at Gladstone Institutes on June 8th, 2022. Photo courtesy Gladstone Institutes.

For years scientists have been touting the potential of CRISPR, a gene editing tool that allows you to target a specific mutation and either cut it out or replace it with the corrected form of the gene. But like all new tools it had its limitations. One important one was the difficult in delivering the corrected gene to mature cells in large numbers.

Scientists at the Gladstone Institutes and U.C. San Francisco say they think they have found a way around that. And the implications for using this technique to develop new therapies for deadly diseases are profound.

In the past scientists used inactivated viruses as a way to deliver corrected copies of the gene to patients. We have blogged about UCLA’s Dr. Don Kohn using this approach to treat children born with SCID, a deadly immune disorder. But that was both time consuming and expensive.

CRISPR, on the other hand, showed that it could be easier to use and less expensive. But getting it to produce enough cells for an effective therapy proved challenging.

The team at Gladstone and UCSF found a way around that by switching from using CRISPR to deliver a double-stranded DNA to correct the gene (which is toxic to cells in large quantities), and instead using CRISPR to deliver a single stranded DNA (you can read the full, very technical description of their approach in the study they published in the journal Nature Biotechnology).

Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and the senior author of the study, said this more than doubled the efficiency of the process. “One of our goals for many years has been to put lengthy DNA instructions into a targeted site in the genome in a way that doesn’t depend on viral vectors. This is a huge step toward the next generation of safe and effective cell therapies.”

It has another advantage too, according to Gladstone’s Dr. Jonathan Esensten, an author of the study. “This technology has the potential to make new cell and gene therapies faster, better, and less expensive.”

The team has already used this method to generate more than one billion CAR-T cells – specialized immune system cells that can target cancers such as multiple myeloma – and says it could also prove effective in targeting some rare genetic immune diseases.

The California Institute for Regenerative Medicine (CIRM) helped support this research. Authors Brian Shy and David Nguyen were supported by the CIRM:UCSF Alpha Stem Cell Clinic Fellowship program.

Stem Cell Agency Expands Industry Alliance Program to  Accelerate Therapies

An ever-growing array of academic and industry resources are required to rapidly translate scientific discoveries and emerging technologies toward safe and effective regenerative medicine therapies for patients. To help, the California Institute for Regenerative Medicine (CIRM) is creating a network of Industry Resource Partners (IRP) that will make its unique resources available to help accelerate the progression of CIRM-funded Discovery, Translational and Clinical stage research projects toward transformative regenerative medicine therapies for rare and prevalent diseases.

The Industry Resource Partners will offer their services, technologies and expertise to CIRM-funded projects in a cost-effective, stage-appropriate and consistent manner.

For example, Novo Nordisk is making research-grade vials of its Good Manufacturing Practice (GMP)-grade human embryonic stem cell line available for CIRM Discovery Quest stage research projects at no cost. Having access to clinically compatible pluripotent stem cell lines such as this one will help CIRM researchers accelerate the translation of their therapeutic discoveries toward clinical use. Researchers will also have future access to Novo Nordisk’s GMP seed stock as well as opportunities for partnering with Novo Nordisk.

“CIRM is a lender of first resort, supporting projects in the very early stages, long before they are able to attract outside investment,” says Shyam Patel, PhD, the Director of Business Development at CIRM. “With the launch of this program we hope to create a force-multiplier effect by bringing in industry partners who have the resources, experience and expertise to help further accelerate CIRM-funded regenerative medicine research projects.”

This new network builds on work CIRM started in 2018 with the Industry Alliance Program (IAP). The goal of the IAP was to partner researchers and industry to help accelerate the most promising stem cell, gene and regenerative medicine therapy programs to commercialization. Four of the members of the IAP are also founding members or the IRP.

In addition to Novo Nordisk, the IRP includes:

ElevateBio is providing access to high quality, well-characterized induced pluripotent stem cell (iPSC) lines to CIRM Discovery Quest stage research projects for product development in regenerative medicine. CIRM awardees will also have access to ElevateBio’s viral vector technologies, process development, analytical development, and GMP manufacturing services.

Bayer is offering to support the cell therapy process development and GMP manufacturing needs of CIRM Translational and Clinical awardees at its newly built Berkeley facilities. The partnered projects will have access to Bayer’s cell therapy manufacturing facilities, equipment, resources and expertise. Bayer is also open to partnering from fee-based-services to full business development and licensing opportunities. 

Resilience is providing access to its GMP manufacturing services for CIRM Translational and Clinical Stage projects. In addition to providing access to its cell therapy manufacturing services and partnering opportunities, Resilience will provide project consultation that could aid CIRM applicants in drafting manufacturing plans and budgets for CIRM applications.

“These partnerships are an important step forward in helping advance not only individual projects but also the field as a whole,” says Dr. Maria T. Millan, President and CEO of CIRM. “One of the biggest challenges facing regenerative medicine right now involves manufacturing. Providing researchers with access to high quality starting materials and advanced manufacturing capabilities is going to be essential in helping these projects maintain high quality standards and comply with the regulatory frameworks needed to bring these therapies to patients.”

While the IRP Network will offer its services to CIRM grantees there is no obligation or requirement that any CIRM awardee take advantage of these services.

Celebrating academic success and overcoming obstacles

Congratulations to Yasmine Arafa (she/hers), a CIRM Bridges Student Intern at UC Davis Institute for Regenerative Cures! She recently graduated from California State University-Sacramento, officially concluding her Master’s degree and Fulbright Association journey. She conducted research with the aim of developing new therapeutic approaches for rare diseases.

Yasmine says, “I have finally passed my thesis defense and am now a Master‘s degree holder. People in grad school tend to not celebrate their achievements as much, but I chose to celebrate mine.”

“As a graduate student who started their degree in 2020, it has been a rough journey for me. Coming to a new country on my own, away from my family and loved ones, during a pandemic, has been quite the challenge. I‘m proud of myself and of this achievement, because I know the immense amount of academic and mental effort I had to put in to get to this point. To all graduate students out there, don‘t forget to celebrate your success!”

Congrats, Yasmine! She joins 1,663 CIRM Bridges alumni who are helping build the next generation of scientists and meet CIRM’s mission to #AccelerateWorldClassScience here in California for the world. 

To learn more about CIRM’s internship programs, visit our website.

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

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

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  

Creating a ‘bespoke’ approach to rare diseases

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

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.”

The bootcamp helping in the fight against rare diseases

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

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.