Commentary
Video
Need for Better, More Specific Delivery Methods for Gene Therapies in Muscular Dystrophy: Melissa Spencer, PhD
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The professor in residence at UCLA Health provided clinical insight on the limitations of certain gene therapy vehicles for muscular dystrophies, and the need for better vectors that are more myotropic. [WATCH TIME: 3 minutes]
WATCH TIME: 3 minutes
"MyoAAV vectors work well at lower doses and are less tropic to the liver. By de-targeting the liver, you have more available for muscle, as the liver acts as a huge sink for AAV. Targeting muscle stem cells is crucial for long-lasting therapy, especially with CRISPR, because a permanent gene edit in these cells could improve the durability of the treatment."
Duchenne muscular dystrophy (DMD), a severe and progressive muscle-wasting disease, has historically been managed through supportive treatments aimed at improving quality of life, delaying disease progression, and managing complications. Over the years, the number of new disease-modifying treatments for DMD has expanded, capped off by the 2023 approval of Elevidys (Sarepta), the first gene therapy for patients living with the disease. An adeno-associated virus (AAV) vector-based gene therapy, the drug originally was approved through the accelerated approval pathway and was later switched to traditional approval shortly after.
While gene therapies hold a lot of promise for muscular dystrophies, there are a lot of questions to be answered about their long-term benefit, as well as the feasibility and function of effectively dosing patients who need them. At the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, one presentation focused on emerging approaches to treating genetic muscular dystrophies. Given by Melissa Spencer, PhD, the talk focused on AAV, a delivery vehicle used to transport nucleic acids into the body for gene therapies, and how effective this strategy is.
Spencer, a professor of residence at UCLA Health, also covered the difficulty of assessing function or functional benefits in DMD. Following her talk, she sat down with NeurologyLive® to discuss delivery methods for gene therapy, emphasizing the need for more effective and specific routes, particular with vectors that are myotropic and less prone to being absorbed by the liver. In the discussion, she highlighted promising developments in AAV technology, including MyoAAV vectors, which are optimized for muscle targeting and require lower doses. Furthermore, she touched on the ongoing challenges in targeting muscle stem cells for long-term, durable treatments, particularly using CRISPR.
