Gene therapy using adeno-associated virus (AAV) vectors is transforming care for Duchenne muscular dystrophy (DMD), but patient safety remains the top priority as serious side effects continue to shape how these treatments are used, according to a review published recently in Genes.
“The field of AAV-based gene therapy for DMD is rapidly evolving with tremendous research in the field,” the authors said. “Recent tragic outcomes related to AAV toxicity have continued to shape the field, highlighting the urgent need for more AAV biology-informed and patient-centered considerations in DMD.”
Researchers emphasized that long-term benefit will depend on safer dosing, better patient selection and close monitoring, especially in light of rare but severe complications including liver failure and cardiac events.
These therapies work by delivering a shortened version of the dystrophin gene into muscle cells using a modified virus. The virus has been engineered so it cannot replicate and instead carries therapeutic DNA.
Different versions of this delivery system target muscle and heart tissue with varying efficiency. Because DMD affects the entire body, treatment requires very high doses, often in the range of 1014 to 1016 vector genomes per patient, far higher than doses used for other diseases.
Read more about therapies in DMD
That high dose is a major reason side effects occur. The body can react strongly to the therapy, activating the immune system almost immediately. This can lead to inflammation, liver stress and, in rare cases, life-threatening complications such as thrombotic microangiopathy or severe immune reactions. Symptoms may begin within days to weeks after treatment and can include nausea, fatigue or more serious organ dysfunction.
The underlying disease itself may increase these risks. In DMD, muscles are already inflamed and damaged, and the heart is often weakened. This creates a more fragile environment, making patients, particularly older or nonambulatory individuals, more vulnerable to complications such as myocarditis or cardiogenic shock. Some patients have also experienced immune attacks against the newly produced dystrophin protein, leading to muscle weakness and breathing difficulties weeks after treatment.
Liver injury has become one of the most closely watched risks. While some patients only show mild increases in liver enzymes, others have developed severe liver failure, including fatal cases.
These events have led regulators to restrict certain therapies to younger, ambulatory patients and to require enhanced monitoring before and after treatment. Doctors now carefully evaluate liver health and may involve specialists to manage potential complications early.
For patients and families, these findings mean that gene therapy is neither a cure nor a simple decision. It offers hope for slowing disease progression and improving muscle function, especially when given early, but it also requires weighing meaningful risks. Ongoing research is focused on making these therapies safer by redesigning the viral vectors, lowering immune reactions and identifying which patients are most likely to benefit.
Future approaches, including lower-dose delivery methods and alternative routes such as spinal injection, may reduce risks while expanding access. For now, experts stress that informed decision-making, close follow-up and continued advances in safety will determine how much this promising treatment can truly change the course of DMD.
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