Key Points
- Friedreich ataxia cardiomyopathy (FA-CM) is a fatal condition with no approved therapies targeting the underlying cardiac disease.
- LX2006 (AAVrh.10hFXN) is a gene therapy designed to restore frataxin expression in cardiac tissue.
- In early-phase data, a single intravenous dose increased cardiac frataxin levels and improved cardiac structure and biomarker profiles.
- The therapy was generally well tolerated, with one possibly treatment-related myocarditis event.
Friedreich ataxia (FA) is a rare, progressive, autosomal recessive disorder caused by mutations in the frataxin (FXN) gene, leading to mitochondrial dysfunction and multisystem disease. While neurologic manifestations are prominent, cardiomyopathy remains the leading cause of death in affected patients. Despite advances in neurologic therapies, there are currently no approved treatments targeting the cardiac manifestations of FA.
At the American College of Cardiology 2026 Investigative Horizons III Sessions on March 30, 2026, Dr. Ronald G. Crystal, Chairman of Genetic Medicine at Weill Cornell Medicine, presented early-phase results evaluating LX2006, an adeno-associated virus (AAV)-based gene therapy designed to restore cardiac frataxin expression. The study (NCT05302271) pooled data from two ongoing open-label, dose-escalation Phase 1/2 trials conducted by Weill Cornell Medicine and Lexeo Therapeutics. A total of 17 adult patients with FA-associated cardiomyopathy received a single intravenous infusion of LX2006 across three dose cohorts (1.8×10¹¹, 5.6×10¹¹, and 1.2×10¹² vector genomes/kg). Participants underwent serial assessments of cardiac structure and function using cardiac MRI, circulating biomarkers, and, in a subset, cardiac biopsy to quantify frataxin expression.
LX2006 was generally well tolerated. Across the study population, adverse events were mostly mild and transient. Four serious adverse events were reported, including one case of grade 2 myocarditis occurring at 12 months that was considered possibly treatment-related and resolved with corticosteroid therapy.
Biologically, the therapy demonstrated clear target engagement. Cardiac biopsy data showed dose-dependent increases in frataxin expression at 3 months, with increases up to approximately 115% in the highest dose cohort. These molecular effects translated into favorable cardiac remodeling signals. At latest follow-up, left ventricular mass index (LVMI) decreased in 56% of patients and stabilized in the remainder, with no patients demonstrating worsening hypertrophy, as illustrated in longitudinal imaging analyses.
Cardiac injury biomarkers also improved substantially. High-sensitivity troponin I levels declined in 94% of patients, with mean reductions exceeding 50% overall and even greater reductions among those with elevated baseline values. Functional cardiac measures were largely preserved. Most patients maintained normal left ventricular ejection fraction, while one patient with reduced baseline function experienced marked improvement (35% to 74%) alongside reductions in LV mass and troponin levels. Patient-reported outcomes also suggest clinical benefits. Among those with available data, KCCQ-12 scores improved by an average of +9 points, indicating meaningful gains in health status. Neurologically, stabilization of disease progression was observed using the modified Friedreich Ataxia Rating Scale (mFARS), contrasting with the expected decline seen in untreated patients.
Taken together, these findings suggest that a single administration of LX2006 can restore cardiac frataxin levels and favorably modify key markers of myocardial stress and remodeling in patients with FA cardiomyopathy. Dr. Crystal noted that “these early results demonstrate biologic activity and suggest the potential for gene therapy to directly target the underlying cause of cardiomyopathy in Friedreich ataxia,” while emphasizing the need for larger studies to confirm durability and long-term clinical benefit.