TOPLINE:

An intravenous adeno-associated viral gene therapy delivering the normal frataxin gene (AAVrh.10hFXN) was generally well tolerated in patients with Friedreich ataxia (FA) cardiomyopathy. The therapy increased the levels of cardiac frataxin at 3 months and was linked to preliminary favorable changes.

METHODOLOGY:

• Researchers pooled data from two independent, open-label nonrandomized clinical trials to assess the safety and preliminary efficacy of a single intravenous gene therapy in patients with FA cardiomyopathy.
• They included 17 adults with FA cardiomyopathy who underwent gene therapy at US medical centers, and data were collected between 2022 and 2025. The mean age of the patients was 25 years, and 65% of them were women.
• The normal cardiac frataxin gene was inserted into an adeno-associated viral vector. Patients received one of the three doses of this construct intravenously over 1 hour, along with a 14-week course of prednisone to reduce immune reactions.
• The primary endpoint was safety. Exploratory endpoints included the levels of the frataxin protein, quantified by performing cardiac biopsy; the left ventricular mass index; and the serum levels of high-sensitivity troponin I.
• Patients were followed up for a mean duration of 20 months.

TAKEAWAY:

• The therapy was generally well tolerated, with no deaths reported. Four serious adverse events were recorded — three possibly linked to immunosuppression achieved using prednisone and one possibly linked to vector-related myocarditis — and most other adverse events were mild or resolved.
• The levels of the cardiac frataxin protein increased 3 months after therapy in all eight patients who underwent cardiac biopsy, with greater increases at higher doses.
• The left ventricular mass index decreased or remained stable in most patients. A mean monthly reduction of 0.50 g/m² was observed after excluding a patient with myocarditis.
• Most patients had a ≥ 10% reduction in the levels of high-sensitivity troponin I after therapy.

IN PRACTICE:

“This nonrandomized clinical trial found that intravenous administration of [the gene therapy] was well tolerated and is a potential treatment for FA cardiomyopathy, as evidenced by preliminary improvement in exploratory efficacy endpoints,” the researchers wrote.

SOURCE:

The study was led by Ronald G. Crystal, MD, of Weill Cornell Medical College in New York City. It was published online on June 17 in JAMA Cardiology.

LIMITATIONS:

The sample size was small. The study did not have a separate control group for comparison. Most participants had early cardiac dysfunction, and the effects on patients with a broader spectrum of the disease were not assessed.

DISCLOSURES:

One trial received funding from the National Heart, Lung, and Blood Institute and another from Lexeo Therapeutics. Five authors were affiliated with Lexeo Therapeutics. Several authors reported receiving grants, consulting fees, royalties, salary from; holding stock or stock options in; and having other financial ties with multiple organizations, including the funding organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.