Gene Therapy for Friedreich Ataxia Cardiomyopathy Shows Promise in Early Trial

A phase 1/2 clinical trial evaluating an intravenous adeno-associated viral gene therapy for Friedreich ataxia (FA) cardiomyopathy found the treatment was generally well tolerated, with measurable increases in cardiac frataxin levels and preliminary improvements in heart function, according to a study published in *JAMA Cardiology* on June 17, 2025.

Study Design and Patient Overview

Researchers pooled data from two open-label, nonrandomized trials to assess the safety and early efficacy of AAVrh.10hFXN, a gene therapy delivering the normal frataxin gene. The study included 17 adults with FA cardiomyopathy, with a mean age of 25 years and 65% women, treated at U.S. medical centers between 2022 and 2025. Patients received a single intravenous dose of the therapy over one hour, along with a 14-week course of prednisone to mitigate immune reactions.

Safety and Efficacy Outcomes

The primary endpoint focused on safety, with four serious adverse events reported. Three were possibly linked to prednisone use, while one was associated with vector-related myocarditis. Most other side effects were mild or resolved.

Exploratory endpoints showed encouraging results: cardiac frataxin protein levels increased in all eight patients who underwent biopsy three months post-treatment, with higher doses correlating with greater increases. Left ventricular mass index decreased or stabilized in most participants, and serum high-sensitivity troponin I levels dropped by at least 10% in most cases.

Implications and Limitations

The researchers noted the therapy’s potential as a treatment for FA cardiomyopathy, citing preliminary improvements in biomarkers and cardiac structure. However, the study’s small sample size and lack of a control group limit conclusions. Most participants had early-stage disease, so outcomes in more advanced cases remain unexplored.

Expert Perspective

Ronald G. Crystal, MD, of Weill Cornell Medical College and lead author of the study, emphasized the need for larger, randomized trials to confirm these findings. “This nonrandomized trial suggests intravenous gene therapy is a promising approach, but further research is critical,” he said.

Financial Disclosures and Conflicts

The trials received funding from the National Heart, Lung, and Blood Institute and Lexeo Therapeutics. Five authors had financial ties to Lexeo, including stock ownership and consulting agreements.

What’s Next for FA Cardiomyopathy Treatment?

While the results are preliminary, they highlight the potential of gene therapy to address the underlying genetic cause of FA, a rare disorder characterized by progressive neurological and cardiac damage. Researchers are now exploring longer-term follow-up and broader patient populations.

FAQ: Key Questions About the Study

What is Friedreich ataxia?
Friedreich ataxia is a genetic disorder causing degeneration of the spinal cord and brain, often leading to heart failure.

How does the gene therapy work?
The therapy uses a modified virus to deliver a functional frataxin gene to heart cells, aiming to restore protein levels.

Are there other treatments for FA cardiomyopathy?
Current options focus on managing symptoms, such as heart failure medications. Gene therapy represents a novel, disease-modifying approach.

Conclusion

The study underscores the evolving landscape of gene therapy for genetic disorders, offering hope for FA patients while highlighting the need for rigorous, large-scale research to validate these findings.