New gene therapies for Duchenne muscular dystrophy (DMD) are changing the treatment landscape but come with serious challenges that directly affect patients and families, according to a review published recently in Gene Therapy.
While these therapies aim to slow progression of disease, recent patient deaths, unclear clinical benefits and immune system complications highlight the risks that remain.
“[T]he concept of internally-deleted dystrophin minigene therapies has made the leap from bench to bedside and FDA-approval in the case of Elevidys,” stated the review’s authors. “Multiple other microdystrophin gene therapy clinical programmes are ongoing, and the challenge of addressing DMD remains.”
Elevidys, developed by Sarepta Therapeutics, became the first FDA-approved gene therapy for DMD in 2023. It delivers a shortened version of the dystrophin protein, which normally acts like a shock absorber in muscle. Approval was based on increases in dystrophin levels rather than clear improvements in muscle strength.
In 2024, full approval was granted to Elevidys despite a large study showing no significant benefit on the main mobility measure. Some secondary outcomes, such as the ability to rise from the floor or climb stairs, did improve.
Read more about therapies for DMD
In 2025, however, two patients treated with Elevidys died of acute liver failure. These tragic outcomes led Sarepta to pause some trials and restrict use in non-ambulatory patients while safety protocols were reassessed.
Pfizer also discontinued its own microdystrophin program after two deaths in clinical trials and failure to show meaningful benefit on walking and strength tests.
For patients and families, these developments mean difficult choices. DMD is a progressive condition that typically leaves boys wheelchair-dependent by age 10 to 12 and shortens life expectancy to the 20s or 30s due to heart and breathing problems. Current standard treatments, such as steroids, can slow the disease but do not stop it. Gene therapy offers the potential to restore part of the missing protein, but the risks include severe immune reactions, liver injury and uncertain long-term durability.
Additional hurdles complicate access. Many people already carry antibodies against the viral vectors used to deliver these therapies, which may block treatment or increase the chance of side effects. Patients with certain gene deletions are also excluded from trials because of higher risk of immune complications. Even when patients qualify, therapy is given only once, and it remains unknown how long the benefit lasts.
Despite setbacks, research continues. Companies including Solid Biosciences, Genethon, REGENXBIO and Insmed are testing alternative approaches. For now, patients and caregivers must carefully weigh the potential for improved mobility against the possibility of life-threatening events. Ongoing trials and long-term follow-up will be critical in determining whether these treatments can deliver lasting, safe improvements for people living with DMD.
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