In patients with Friedreich ataxia (FA) cardiomyopathy, intravenous administration of AAVrh.10hFXN, an rh.10 serotype cardiotropic adenoassociated virus vector expressing the normal human FXN coding sequence, was well tolerated and showed promise as a potential treatment, according to findings from a recent nonrandomized clinical trial published in JAMA Cardiology.

Ronald G. Crystal, MD, et al., included 17 patients with FA cardiomyopathy (mean age 25 years, 65% female) who were divided into three dosing groups (1.8 × 10¹¹, 5.6 × 10¹¹ and 1.2 × 10¹² vector genomes per kilogram of body weight). The primary outcome was safety while several exploratory endpoints were also considered, including cardiac biopsy levels of FXN protein, cardiac MRI-derived left ventricular mass index (LVMI) and serum high-sensitivity troponin I.

Over a mean follow-up period of 20 months, four serious adverse events occurred. Three were potentially due to prednisone immunosuppression and one possibly from vector-related myocarditis at 12 months post therapy. All four serious adverse events were resolved.

The authors noted higher levels of cardiac FXN among the eight patients that underwent cardiac biopsy three months post therapy (dose cohort 1: 20%, cohort 2: 81%, cohort 3: 123%), while LVMI decreased by at least 10% in nine patients and stabilized in eight. After excluding the patient that developed myocarditis, they also found that serum high-sensitivity troponin I was lower by at least 10% in 15 patients after therapy; however, it was higher by at least 10% in two study participants.

"AAVrh.10hFXN therapy was associated with stabilization of the [modified FA Rating Scale] neurologic scale score, suggesting that the gene therapy may also be therapeutic for the musculoskeletal and/or neurologic manifestations of FA," add the authors. "Comparing this in treated patients vs. untreated control individuals is of interest for future study."