A new gene therapy for Friedreich ataxia cardiomyopathy appears safe and shows early signs of reversing heart damage, according to a phase 1 clinical trial published June 17 in JAMA Cardiology. Researchers at Weill Cornell Medicine found that an intravenous infusion of a healthy FXN gene reduced heart wall thickness and lowered markers of cardiac injury in trial participants.
How the FXN Gene Therapy Works
The experimental treatment uses an adeno-associated virus as a delivery vehicle to restore the function of the FXN gene. According to Dr. Ronald G. Crystal, lead author and chair of the Department of Genetic Medicine at Weill Cornell Medicine, the virus is engineered to travel specifically to the heart. Once delivered, the healthy gene aims to boost levels of the frataxin protein, which is essential for cellular energy production. In patients with Friedreich ataxia, a genetic variant causes a deficiency in this protein, leading to energy-starved cells and the thickening of heart walls, a condition known as hypertrophic cardiomyopathy.
Did you know? While Friedreich ataxia is often associated with neurological symptoms like balance and speech difficulties, heart disease is the primary cause of death for up to 65 percent of patients, according to study estimates.
Clinical Trial Results and Efficacy
The study pooled data from 17 patients across two independent trials—one led by Weill Cornell Medicine and another by Lexeo Therapeutics. Patients received a one-hour infusion and were monitored for up to 36 months. Results showed that all eight patients in the Lexeo cohort experienced an increase in frataxin protein levels in cardiac tissue after three months. Furthermore, MRI scans indicated a decrease in left ventricular mass index, suggesting a reduction in the dangerous heart wall thickening characteristic of the disease. Researchers also observed a drop in troponin I levels, a protein released into the blood when heart muscle is damaged.
How This Therapy Compares to Current Standards
Until recently, therapeutic options for Friedreich ataxia were limited to symptom management. The FDA has approved only one drug, Skyclarys (omaveloxolone), which focuses on slowing the progression of neurological symptoms. Unlike Skyclarys, the new gene therapy targets the underlying genetic cause of the disease. While Skyclarys addresses the neurological impact, the FXN gene therapy specifically seeks to correct the energy deficit in cardiac muscle cells. Dr. Crystal noted that because the current trial focused on early-stage cardiomyopathy, future research will need to evaluate the therapy’s impact on patients with more advanced heart disease.
Pro Tip: Monitoring Cardiac Health
Patients diagnosed with hereditary conditions like Friedreich ataxia should maintain regular screenings with a cardiologist. Early detection of hypertrophic cardiomyopathy allows for more effective intervention, regardless of whether a patient is a candidate for emerging gene therapies.
Frequently Asked Questions
- What is the primary cause of death in Friedreich ataxia patients?
- Heart disease is the leading cause of mortality, accounting for up to 65 percent of deaths in this patient population, according to data cited in the JAMA Cardiology report.
- Is this gene therapy FDA-approved?
- No. The treatment is currently in the phase 1 clinical trial stage. Dr. Crystal stated that the research team’s ultimate goal is to pursue FDA approval based on further efficacy and safety data.
- How is the gene therapy administered?
- The therapy is delivered via a one-hour intravenous infusion, which allows the viral vector to transport the healthy FXN gene to the heart tissue.
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