A phase 1 clinical trial led by Weill Cornell Medicine researchers announced on June 17 that a new gene therapy appears to be safe for patients with Friedreich ataxia cardiomyopathy, a progressive and fatal inherited cardiac disease. The treatment may also reduce heart damage, though further research is needed.
The results, published in JAMA Cardiology, showed that an intravenous infusion of a healthy frataxin (FXN) gene was generally well tolerated and demonstrated early signs of efficacy. These included decreased heart wall thickness—an indicator of cardiomyopathy—and reduced levels of troponin I, which signals heart damage.
"This is a fatal disease, but this is a potential therapy, and our goal is FDA-approval," said Dr. Ronald G. Crystal, the study's lead author and professor at Weill Cornell Medicine, as well as pulmonologist at NewYork-Presbyterian/Weill Cornell Medical Center.
Friedreich ataxia results from variants in the FXN gene that cause low levels of the FXN protein necessary for cellular energy production. "The two most energy consuming organs in the body are your brain and the heart, so the disease is primarily a brain and heart disease," Crystal said. It is an autosomal recessive hereditary disorder affecting up to one in 50,000 people in the United States. Nervous system symptoms often begin in childhood with issues related to balance, walking, and speaking; however, most patients develop heart disease leading to death in up to 65 percent of cases due to hypertrophic cardiomyopathy.
Currently only one other drug—Skyclarys (omaveloxolone)—is approved by the U.S. Food and Drug Administration for treating Friedreich ataxia; it slows neurological progression but does not address its genetic cause.
The study pooled data from two independent studies involving 17 patients: nine from Weill Cornell Medicine funded by National Heart Lung Blood Institute and eight from Lexeo Therapeutics—a company founded by Crystal with support from Weill Cornell Medicine Enterprise Innovation. Patients received a one-hour infusion of gene therapy followed by evaluation over six to thirty-six months across three dose groups.
Overall safety was confirmed with four serious adverse events—all resolved—including three possibly related to prednisone used for immunosuppression during treatment. In Lexeo’s study arm, biopsies revealed increased frataxin protein levels post-treatment while MRI measurements indicated reduced left ventricular mass index—a sign of therapeutic benefit against cardiomyopathy—and lower troponin I levels typically elevated among these patients.
Using the modified Friedreich Ataxia Rating Scale (mFARS), some neurological components stabilized though it remains unclear if this resulted directly from gene therapy effects on skeletal muscle or brain tissue. "But we're unsure whether this was related to the gene therapy reaching the skeletal muscle or the brain," Crystal said. The researchers plan future studies including participants with varying severity of cardiac involvement.
