Genethon Reports Long-Term Efficacy of AAV8 Gene Therapy GNT0004 in Duchenne Muscular Dystrophy

EVRY, France–(BUSINESS WIRE)–March 11, 2026 —

Genethon has announced new clinical data demonstrating the long-term efficacy of its AAV-based gene therapy GNT0004 for Duchenne muscular dystrophy (DMD). The results were presented at the Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Orlando, highlighting sustained clinical benefits in patients treated during the dose-escalation phase of an international multicenter trial sponsored by the company.

The clinical trial enrolled ambulatory boys aged 6 to 10 with Duchenne muscular dystrophy. During the dose-escalation phase, five patients received the AAV gene therapy GNT0004, including four treated in France and one in the United Kingdom. Two patients received the initial dose, while three received the higher therapeutic dose of 3×10¹³ vector genomes per kilogram (vg/kg). Long-term follow-up of the three patients treated at the therapeutic dose demonstrated sustained efficacy, continued pharmacodynamic activity, and a favorable safety profile when administered alongside temporary prophylactic immunosuppression.

Two years after a single intravenous administration of the AAV8 gene therapy, treated patients showed significant improvements in motor function. On the North Star Ambulatory Assessment (NSAA) scale, patients experienced an average increase of 9 points, compared with matched untreated patients from the same clinical centers. This improvement exceeds the threshold considered clinically meaningful. Additional functional assessments also demonstrated clinical benefit, including improvements in walking performance, with a 173-meter advantage in the 6-minute walk test and a 0.95 m/s increase in speed during the 10-meter walk test compared with untreated cohorts.

Biomarker analysis further supported the therapeutic effect of the AAV gene therapy. Creatine phosphokinase (CPK), a marker of muscle damage, decreased by approximately 70% two years after treatment, indicating sustained stabilization of muscle cell membranes. Imaging data from quantitative MRI also showed a more than 18% difference in muscle fat fraction, suggesting a meaningful slowdown in disease progression compared with natural history cohorts.

Importantly, no serious adverse events were reported, supporting the safety profile of the therapy in this early cohort.

Based on these encouraging results, regulatory authorities including the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) have authorized the pivotal phase of the clinical trial. The randomized, double-blind, placebo-controlled study began in September and will enroll 64 ambulatory boys aged 6 to 10 across multiple international sites.

GNT0004 is designed as an AAV8-mediated gene replacement therapy that delivers an optimized hMD1 micro-dystrophin transgene, a shortened but functional version of the dystrophin gene missing in patients with Duchenne muscular dystrophy. The therapy uses a muscle-specific Spc5-12 promoter to drive expression in skeletal muscle and cardiac tissue following a single systemic intravenous infusion.

The gene therapy was developed by Genethon, with preclinical contributions from teams led by Prof. Dickson at Royal Holloway, University of London, the Institute of Myology in Paris, and INSERM / University of Nantes / Nantes University Hospital.

If successful, GNT0004 could represent a promising AAV gene therapy approach for Duchenne muscular dystrophy, potentially offering durable functional improvement with a single treatment.