Mechanism of Action of SRP-9001, A Gene Therapy For Duchenne Muscular Dystrophy
Lisa Borland, Vice President of Global Medical Affairs at Sarepta Therapeutics, discusses the mechanism of action of SRP-9001, an investigational gene transfer therapy for Duchenne muscular dystrophy.
Duchenne muscular dystrophy is the most common and most severe form of muscular dystrophy. It is caused by mutations in the DMD gene that lead to loss of dystrophin and progressive muscle loss. Symptoms of muscle loss most often appear between the ages of 3 to 5 years, and most children with this disease will be wheelchair dependent by their early teens.
Ms. Borland discusses SRP-9001’s mechanism of action in terms of its 3 essential components, its vector, promoter, and transgene. She begins by explaining that SRP-9001 uses AAVrh74 as a vector, which was selected for its tissue selectivity for skeletal and cardiac muscle, as well as its low potential for pre-existing antibodies. She goes on to say that the promoter used in the SRP-9001 construct is MHCK7, which has been shown to drive expression in skeletal and cardiac muscles with minimal or undetectable expression in off-target tissues. Finally, Ms. Borland notes that, as the DMD gene is one of the largest in the human genome, the transgene is a uniquely designed micro-dystrophin-encoding gene.
SRP-9001 is being evaluated in a clinical development program that currently includes 4 clinical trials: Study 101, Study 102, Study 103 (ENDEAVOR), and Study 301 (EMBARK). Data from this program supported the U.S. Food and Drug Administration’s decision to accept and file a Biologics License Applications (BLA) for SRP-9001, which has a regulatory action date of May 29, 2023.
For more information about Duchenne muscular dystrophy and other rare musculoskeletal diseases, visit checkrare.com/diseases/musculoskeletal
