AN EXPERIMENTAL gene therapy has safely shrank or steadied the heart muscle damage that drives most deaths in Friedreich ataxia, an early 17-patient trial reports, offering the first human signal that the approach might treat this fatal inherited disease.
Friedreich ataxia (FA) is a fatal, inherited disorder caused by faults in the frataxin (FXN) gene, producing progressive nerve and heart damage. Cardiomyopathy is the leading cause of death. In FXN-deficient mice, a cardiotropic vector carrying the normal human FXN gene had reversed the heart disease, prompting this first human test.
Pooling Two Dose-Escalation Trials
The non-randomised trial pooled two independent, open-label, dose-escalation studies that used the same vector, AAVrh.10hFXN, and similar protocols at academic medical centres. Seventeen adults with FA cardiomyopathy (mean age 25 years; 65% female) received a single intravenous infusion across three escalating dose cohorts, ranging from 1.8 × 10^11 to 1.2 × 10^12 vector genomes per kilogram.
There were four serious adverse events: three possibly linked to prednisone immunosuppression and one possible vector-related myocarditis at 12 months, all of which resolved. Remaining adverse events were transient, non-serious, or unrelated to treatment. All eight patients biopsied at three months showed higher cardiac frataxin, rising with dose from 20% in the lowest cohort to 81% and 123% in the higher cohorts. LVMI fell by at least 10% in nine patients and stabilised in eight. Excluding the patient with myocarditis, serum high-sensitivity troponin I dropped by at least 10% in 15 patients and rose by at least 10% in two.
The authors concluded that intravenous AAVrh.10hFXN was well tolerated and may offer a potential treatment for the cardiomyopathy of Friedreich ataxia, with early improvements across exploratory efficacy measures. Because the trial was small and uncontrolled, they stressed these signals are preliminary, and that larger randomised trials are needed to confirm whether the therapy meaningfully alters the course of Friedreich ataxia.
Reference
Crystal RG et al. AAVrh.10hFXN gene therapy for the cardiomyopathy of friedreich ataxia: a nonrandomized clinical trial. JAMA Cardiol. 2026;DOI:10.1001/jamacardio.2026.1699.
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