Commentary
Video
Challenges in Identifying Optimal Candidates for Muscular Dystrophy Gene Therapies: Melissa Spencer, PhD
Author(s):
The professor in residence at UCLA Health discussed the critical considerations when deciding appropriate patients for gene therapies, specifically AAV vectors, in treating muscular dystrophies. [WATCH TIME: 4 minutes]
WATCH TIME: 3 minutes
"We definitely need more standardized assays to determine who has pre-existing immunity... because if a person was exposed to wild type AAV... they’re not going to have circulating antibodies."
Duchenne muscular dystrophy (DMD), the most common childhood muscular dystrophy, is an X-linked recessive disorder caused by mutations in the dystrophin gene. Traditionally, the disorder has been treated with corticosteroids; however, there has been recent interest in gene-based approaches. Two promising strategies have emerged: functional miniaturization of dystrophin that can fit into recombinant adeno-associated virus (rAAV) and vascular delivery that allows for a wider distribution of therapeutic gene.
AAV, the delivery vehicle used to transport nucleic acids into the body for gene therapies, was a topic of conversation at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia. In a talk presented at the meeting, Melissa Spencer, PhD, highlighted emerging approaches to treating genetic muscular dystrophies, including the pros and cons behind AAVs. In addition, she also covered the paradox of assessing function in DMD, and when patients may start to see early declines.
Spencer, a professor in residence at UCLA Health, sat down with NeurologyLive® at the meeting to discuss some of the complications with gene therapy trials and the patients being tested. Emphasizing patient selection, she highlighted the need for advanced, standardized assays to better screen for immune responses, especially memory responses to AAV exposure. Spencer also raised concerns over immune complications, such as antibody production and complement system activation, potentially affected by factors like past viral infections. Looking forward, Spencer emphasized the need for improved AAV vectors, particularly for targeting both muscle and stem cells, as well as for better preclinical models that mimic human immune responses to AAV.
