John Brandsema, MD, on the Roadblocks Faced by Gene Therapies for Muscular Dystrophies

"Gene therapy would be the first thing that we would be offering that is disease-modifying, which is a transformative thing when it happens, of course, but we haven’t really had that so much yet."

The past decade has seen transformative advancements in the treatment of neuromuscular disorders, particularly the emergence of gene-based therapies. Approaches such as antisense oligonucleotides, small interfering RNAs, and gene replacement therapies—designed to modulate genes, mRNA, and proteins—have shown significant potential for patients. Notably, 2 major gene therapy approvals have shaped the field: onasemnogene abeparvovec-xioi (Zolgensma; Novartis) for spinal muscular atrophy (SMA) and delandistrogene moxeparvovec-rokl (Elevidys; Sarepta) for Duchenne muscular dystrophy (DMD).

According to the National Center for Advancing Translational Sciences, an estimated 30 million people in the US are affected by a rare disease, with 95% of these conditions lacking an FDA-approved treatment. Many of these diseases result from single-gene mutations, making them strong candidates for gene therapy and fueling optimism for more effective and lasting treatment options. Although, despite the promise of gene therapy, several obstacles remain: securing funding for clinical trials, determining patient eligibility, assessing the optimal timing for intervention, and evaluating potential interactions with other treatments.

Ahead of the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, scheduled for March 16-19 in Dallas, Texas, John Brandsema, MD, one of the chairs of the meeting, shared insights on the hurdles facing gene therapy in neuromuscular disorders with our sister publication, NeurologyLive. As the leader of the “Gene Therapy Updates” session, he emphasized the critical need to identify the right candidates for treatment, particularly in conditions with multiple therapeutic options. Brandsema, a pediatric neurologist at Children’s Hospital of Philadelphia, also highlighted how newborn screening could transform treatment strategies, citing SMA as an example of how early intervention leads to better outcomes. Additionally, he addressed the complexities of determining the ideal timing for gene therapy, particularly in diseases like DMD, where factors such as age and disease progression play a crucial role in treatment decisions.

Registration for the 2025 MDA Conference is now open! The meeting is set to be held at the Hilton Anatole, Dallas, Texas, from March 16 to 19, 2025. To register and for more information, head to: www.mdaconference.org