DALLAS—A new gene therapy, delandistrogene moxeparvovec, has shown promise in slowing or stabilizing Duchenne muscular dystrophy (DMD) in boys 4 to 8 years old, according to results from a phase 3 clinical trial.
The findings were presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference by Crystal Proud, MD, from the Children’s Hospital of The King’s Daughters in Norfolk, Virginia.
Delandistrogene moxeparvovec is the first gene therapy approved in the U.S. for treating DMD. It is currently approved for boys 4 to 5 years old who have a confirmed mutation in the dystrophin gene. The therapy works by delivering a shortened version of the dystrophin protein, called microdystrophin, which people with DMD are unable to produce. This protein helps support muscle function.
The study was conducted in two parts. First, some boys received the gene therapy while others received a placebo (a treatment with no active working drug). The second part involved giving the gene therapy to those who initially received the placebo. Since all participants eventually received the treatment, researchers compared their progress to a separate control group outside the study,
Muscle biopsies showed that the therapy continued to be effective in the long term. The amount of microdystrophin in muscle tissue increased from 34.29% at the start of treatment to 45.68% after 64 weeks. These results suggest that the therapy continues to support the production of functional dystrophin, which is needed to stabilize DMD.
Functional improvement
The North Star Ambulatory Assessment (NSAA) is a test used to measure overall muscle function in young boys with DMD. The study found that the treated group improved their NSAA score by 2.63 points, while the control group’s score worsened by 0.25 points.
In the Time to Rise test, which measures how long it takes a person lying on their back to stand up, the treated group improved by 0.65 seconds, whereas the control group took 2.71 seconds longer.
Similarly, in the 10-Meter Walk/Run Test, which assesses how quickly a patient can walk or run 10 meters, the treated group’s time decreased by 0.04 seconds, while the control group decreased by 1.32 seconds.
Safety and side effects
A total of 34 adverse events were reported in 15 patients (23.8%), though no participants discontinued treatment, died, or experienced serious side effects related to immune system activation.
The most common adverse events were:
- Increased troponin-I (6.3%)— a protein linked to heart function; elevated levels may indicate cardiac damage
- Proteinuria (3.2%)—high levels of protein in urine, often due to kidney damage
- Increased gamma-glutamyl transferase (3.2%)—a liver enzyme; elevated levels can signal liver or bile duct damage
- Headache (3.2%)
- Nausea (3.2%)
“The most common side effects that we see are nausea with the possibility of vomiting, and that usually has the highest risk within the first one to two weeks. Most of our patients that we see have that [symptom], experience it within the first probably two or three days, if it’s going to happen,” Dr. Proud said, noting that the other side effects “are much less likely.”
“The thing that’s probably going to impact the need for some sort of management is if we see some liver inflammation,” she said. “We mitigate that by adjusting steroid dosing.”
One patient experienced two serious cases of rhabdomyolosis—a rare condition that causes muscle breakdown—but recovered both times.
Future research
Following the relative success of this clinical trial, Proud and her team are looking forward to another trial to test delandistrogene moxeparvovec further.
“I’m so enthusiastic about the potential opportunities that we have utilizing delandistrogene moxeparvovec,” Dr. Proud said. “We’re continuing an investigation in older boys and nonambulatory boys, and so it’s going to be really exciting to eventually see those results to make sure that we’re seeing the efficacy and the safety and tolerability that we hope to see.”
