A one-time gene therapy appeared to stabilize or improve function in boys with Duchenne muscular dystrophy (DMD), offering early evidence that the treatment may slow the disease’s usual progression, according to a study to be presented at the Muscular Dystrophy Association’s 2026 Clinical and Scientific Conference.
In long-term follow-up from a small phase 1/2 trial, boys who received the selected dose maintained better muscle performance than expected based on natural history data, without serious adverse reactions. Researchers say the findings must be confirmed in an ongoing phase 3 study.
The therapy, called GNT0004, is an adeno-associated virus 8-based gene therapy designed to deliver a shortened but functional version of dystrophin, the protein missing in DMD. It uses a Spc5.12 promoter to target skeletal and heart muscle. The treatment is being studied in the international all-in-one phase 1/2/3 clinical trial GNT-016-MDYF, which includes dose escalation, a placebo-controlled pivotal phase 3 portion and long-term follow-up.
Ambulatory boys aged 6 to 10 years who were taking stable corticosteroids were eligible if their North Star Ambulatory Assessment (NSAA) scores were stable or beginning to decline. Participants also had to be followed for at least six months in a separate natural history study, GNT-014-MDYF, allowing researchers to compare outcomes with boys who did not receive gene therapy.
Read more about therapies for DMD
Five patients enrolled in the first part of the study and three received dose 2, defined as 3 ✕ 10¹³ vector genomes per kilogram. This dose was selected for further testing. At week 8, muscle biopsies showed a mean of 53% of fibers were positive for the new dystrophin protein. Blood levels of creatine kinase, a marker of muscle damage, fell from a mean of 19,175 IU/L at baseline to 4,037 IU/L at 18 months, a 79% decrease that persisted over time.
Functionally, treated boys remained stable or improved compared with expected decline in the natural history group. At one year, the difference was 4.7 points on the NSAA scale and 0.1 meters per second in stride velocity at the 95th centile, both exceeding the minimal clinically important difference and reaching statistical significance for NSAA.
“These differences exceed their respective Minimal Clinically Important Difference,” explained this study’s authors.
No serious adverse reactions were reported at dose 2.
For patients and families, these early results suggest the possibility of slowing muscle loss and preserving mobility for longer. However, because only three boys received the selected dose, larger and longer studies are needed to confirm safety and effectiveness before the therapy could become widely available.
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