The California Institute for Regenerative Medicine (CIRM) has awarded $7.4 million to support a University of California San Diego team developing a first-of-its-kind stem cell-based gene therapy for Friedreich's ataxia, a rare inherited neurodegenerative disease that causes progressive loss of coordination, muscle strength, heart function and overall mobility. The new funding will help the research team complete the final steps required by federal regulators before they can apply to begin a first-in-human clinical trial.
This support is essential for scientific progress and for families living with Friedreich's ataxia. The grant enables us to finish the safety studies and manufacturing work we must complete before submitting an Investigational New Drug application to the Food and Drug Administration. Each step brings us closer to being able to test this therapy in people for the first time and, ultimately, closer to hopefully changing the course of this devastating disorder."
Stephanie Cherqui, PhD, professor of pediatrics at UC San Diego School of Medicine and principal investigator on the award
Friedreich's ataxia, while rare, affects tens of thousands of people in the United States and is caused by a genetic defect that reduces production of a protein called frataxin, which cells need to maintain healthy function, particularly in the nervous system and heart. There is currently no cure, and available treatments do not prevent long-term decline. Most individuals diagnosed in childhood or adolescence experience increasing mobility challenges and shortened life expectancy.
The team will pursue an approach that uses a person's own blood-forming stem cells, removes the genetic flaw with a gene-editing technology (CRISPR-Cas9), and then returns the corrected cells to the patient. The goal is for those repaired cells to settle into the bone marrow and then migrate into tissues throughout the body and restore healthy levels of frataxin, providing benefit over the long term without the need for repeated dosing.
This new award supports a series of practical but essential steps required before regulators will authorize testing the treatment in clinical trial participants. These include studies in animals to confirm safety; additional testing to show that the precise genetic correction does not introduce unwanted changes elsewhere in the DNA; and continued work to ensure that the modified cells can be manufactured at clinical-grade quality and at a scale suitable for human treatment. The project will also finalize the clinical trial design, identify clinical sites and develop plans to ensure patient access if the therapy eventually proves safe and effective.
The UC San Diego team has spent more than a decade developing the scientific foundation for this approach. In early studies, the scientists showed that when healthy stem cells were transplanted into animal models of Friedreich's ataxia, they migrated into the nervous system, muscle, and heart and delivered healthy frataxin to the affected cells. Those experiments prevented nerve and heart damage. More recent work has shown that gene-edited human stem cells can repair the underlying defect in cells grown in the laboratory and improve survival of neurons, while also reducing damaging inflammation associated with the disease.
The award also responds to a long-standing need within the Friedreich's ataxia community. Because the condition impairs many parts of the body, including the brain, spinal cord, heart and pancreas, an ideal therapy would be one that can reach multiple organs. The hope behind this approach is that transplanting a patient's own repaired stem cells will allow those cells to disperse throughout the body, deliver frataxin where it is needed, and provide a long-lasting effect after a single procedure.
CIRM previously funded foundational work by Cherqui and colleagues in 2022, supporting the early stages of development and providing data that helped guide today's award. The new funding is designed to move the program through its final pre-clinical stage and toward a formal application to the Food and Drug Administration.
If the program reaches the point of an approved clinical trial, it would become the first-ever test of a gene-edited stem cell therapy for Friedreich's ataxia in humans. For patients and families who have watched the disease progress for generations, the UC San Diego team hopes this marks the beginning of a new chapter - one focused on directly repairing the genetic cause of the disease rather than treating symptoms after the fact.
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