Although a phase 3 trial for the gene therapy delandistrogene moxeparvovec did not meet its main goal of improving movement scores in Duchenne muscular dystrophy (DMD), other measurements suggested the treatment helped slow disease progression and improve muscle integrity.
The findings were presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference by Krista Vandenborne, Ph.D., from the University of Florida College of Public Health and Health Professions.
How the therapy works
In DMD, the lack of working dystrophin protein makes muscles more likely to break down and repeatedly attempt to repair themselves. Over time, muscles lose their ability to heal properly and are gradually replaced by fat and scar-like tissue. Delandistrogene moxeparvovec is designed to counter this process by delivering a working version of dystrophin to muscle cells.
About the study
The trial included 125 boys aged 4 to under 8 years, but only 39 from the first part of the study underwent additional magnetic resonance (MR) imaging to assess muscle changes. MR imaging is a noninvasive tool that uses a strong magnetic field to create detailed images of the body, helping researchers monitor disease progression. In this study, MR scans measured fat buildup and muscle health.
Read more about the study and delandistrogene moxeparvovec
Fat buildup results
Fat buildup in muscles is measured as muscle fat fraction. As DMD progresses, muscle is gradually replaced by fat, making this an important marker of disease severity.
“Muscle fat fraction has been shown to strongly correlate with functional endpoints and predict a loss of function in Duchenne,” Vandenborne explained. “It’s well established . . . that muscle fat fraction, which essentially measures the loss of muscle and its replacement by fat, increases [with] the course of age and disease progression in Duchenne.”
Researchers focused on two key muscles used for walking—the calf and outer thigh. At the start of the study, these muscles had low fat levels, meaning they were still relatively unaffected by DMD. After 52 weeks, fat buildup had increased in all participants, but the increase was smaller in those who received the gene therapy, suggesting the treatment helped slow disease progression.
Muscle integrity results
Muscle health was assessed using T2 relaxation time, where higher values indicate more muscle damage.
“Muscle T2 increases in Duchenne not only because of the presence of fat infiltration, but it’s also sensitive to muscle damage, inflammation, and edema,” Vandenborne explained. “Muscle T2 is elevated in very young boys . . . prior to any changes in fat fraction.”
The study measured T2 in five muscles: the hamstring, quadriceps, calf, outer thigh, and back of the thigh. After 52 weeks:
- In the untreated group, T2 increased in all five muscles, indicating worsening muscle damage.
- In the treated group, four out of five muscles showed no change or improvement in T2, suggesting better muscle integrity.
A statistical test at 52 weeks confirmed a significant difference between the treated and untreated groups, reinforcing the therapy’s potential to stabilize or slow disease progression.
Study limitations
Vandenborne noted this was a smaller exploratory study with only 39 participants, so further research with a larger group may be needed. However, she did not mention any specific future trials.
