While gene therapy for Duchenne muscular dystrophy (DMD) offers real promise, it must be used with greater care to protect patients from rare yet serious side effects, according to a review published recently in Molecular Therapy.
Researchers now say the main lesson from past tragedies is not that gene therapy should stop, but that safety strategies must improve so benefits outweigh risks.
DMD is caused by the lack of dystrophin, a protein that keeps muscles strong. Without it muscles weaken over time, affecting walking, breathing and the heart. New treatments use adeno-associated virus, or AAV, to deliver a working dystrophin gene.
Many trials of AAV gene therapy have shown improved muscle markers and function. However, several hospitalizations and deaths have occurred across DMD and other genetic diseases after very high doses were given through the bloodstream.
Scientists reviewed these cases and found that timing matters. Some deaths happened within days to weeks due to intense immune reactions that damaged blood vessels. This damage can lead to conditions such as clotting disorders, lung failure or widespread inflammation.
Read more about therapies for DMD
Other deaths occurred months later, often linked to liver failure likely driven by a delayed immune attack on treated cells. A few happened more than a year later with unclear causes, though heart or muscle injury may have played a role.
“Our knowledge of late fatality is extremely limited,” explained this review’s authors.
For patients and families, the most important takeaway is that these outcomes are rare but real. Those with advanced disease or underlying liver or heart stress may be more vulnerable. In DMD, many patients already have fragile muscles, altered blood vessels and changes in liver fat which may increase risk when exposed to very high doses of gene therapy.
The good news is that doctors are learning how to lower these dangers. Careful screening before treatment, close monitoring afterward and early use of immune-suppressing medicines have already prevented deaths in some trials. Researchers are also redesigning the virus itself to better target muscle while avoiding the liver, allowing lower doses to be used.
“A more comprehensive understanding of immunosuppressive regimens is required to optimize the safety and efficacy of AAV gene therapy,” said the authors.
Newer versions of AAV are showing encouraging early results with fewer liver problems and strong dystrophin expression. Experts stress that families should talk openly with care teams about potential risks, benefits and unknowns. As knowledge grows gene therapy for DMD is expected to become safer, giving patients hope not just for longer life but for better quality of life.
Sign up here to get the latest news, perspectives, and information about DMD sent directly to your inbox. Registration is free and only takes a minute.
