Clinically Relevant Challenges and Roadblocks of Gene Therapies for Muscular Dystrophies: John Brandsema, MD

WATCH TIME: 3 minutes

"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."

In the past decade, there has been a real revolution in the therapeutic landscape of neuromuscular disorders. Innovative gene-based therapies, such as antisense oligonucleotides, small interfering RNAs, and gene replacement therapy, which rely upon the modulation of genes, mRNA, and/or proteins, have emerged as potentially promising approaches for patients. To date, the neuromuscular field has seen 2 major gene therapy approvals: onasemnogene abeparvovec-xioi (Zolgensma; Novartis) for spinal muscular atrophy (SMA) in 2019, and delandistrogene moxeparvovec-rokl (Elevidys; Sarepta) for Duchenne muscular dystrophy (DMD).

The National Center for Advancing Translational Sciences has estimated that 1 in 10 individuals (approximately 30 million) in the United States have a rare disease and that 95% of the approximately 10,000 known rare diseases lack an FDA-approved treatment. Many rare diseases are caused by single gene defects, making them potentially amenable to treatment with gene therapy, and providing hope for better and more durable treatments on the horizon. Despite the promise that gene therapy brings to these communities, there are still several challenges to their integration, including funding clinical trials to test novel mechanisms, patient eligibility, timing of treatment, and whether other treatments will interfere with their safety and efficacy.

Prior to the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, set to take place March 16-19 in Dallas, Texas, John Brandsema, MD, a chair of the meeting, sat down to discuss the roadblocks in the ongoing exploration of gene therapy for neuromuscular disorders. Brandsema, who will lead a session on “Gene Therapy Updates,” spoke about the importance of determining the right patient for gene therapy, especially when it comes to diseases that have multiple treatment options available. An expert in the field, Brandsema also discussed how early diagnosis through newborn screening could change treatment strategies, with examples like SMA showing substantial improvement with early intervention. Brandsema, a pediatric neurologist at Children’s Hospital of Philadelphia, touched on the uncertainties with the best timing for gene therapy, especially in diseases like DMD, where real-world factors such as age and disease progression complicate treatment decisions.