UCSD Receives Grant for Gene-Edited Stem Cell Therapy in FRDA

Key Takeaways

• A $7.4 million award supports advancement of a first-of-its-kind stem cell-based gene therapy program for Friedreich's ataxia.
• The approach uses autologous blood-forming stem cells edited with CRISPR-Cas9 and is intended to restore frataxin after reinfusion.

A $7.4 million award from the California Institute for Regenerative Medicine will support a UC San Diego team developing a stem cell-based gene therapy for Friedreich's ataxia. The condition is a rare inherited neurodegenerative disease associated with progressive loss of coordination, muscle strength, heart function, and mobility.

Friedreich's ataxia stems from a genetic defect that reduces production of frataxin, a protein cells need for healthy function, especially in the nervous system and heart. The strategy uses a patient's own blood-forming stem cells, corrects the genetic flaw with CRISPR-Cas9, and reinfuses the repaired cells. Those corrected cells are intended to engraft in bone marrow, migrate into tissues throughout the body, and restore healthy frataxin levels. This approach is intended to provide a long-lasting effect after a single procedure.

The group has spent more than a decade building the scientific foundation for the approach, with earlier support that included $4.8 million in CIRM funding in 2022. In animal models, transplanted healthy stem cells reached the nervous system, muscle, and heart and delivered healthy frataxin to affected cells. Those experiments were also described as preventing nerve damage and damage to the heart. More recent laboratory work with gene-edited human stem cells repaired the underlying defect in lab-grown cells, improved neuron survival, and reduced damaging inflammation.

The new funding supports an integrated package of preclinical and regulatory work before any patient study can begin. That package includes animal safety studies, testing for off-target or other unwanted DNA changes, and clinical-grade manufacturing at a scale suitable for human treatment. It also covers clinical trial design, site identification, and planning ahead of an Investigational New Drug application to the FDA.

Next steps are a formal IND submission and then first-in-human testing if the program advances. If that trial moves forward, it would represent the first human test of a gene-edited stem cell therapy for Friedreich's ataxia.