1. Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials
- Author
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Chamberlain, Jeffrey S, Robb, Melissa, Braun, Serge, Brown, Kristy J, Danos, Olivier, Ganot, Annie, Gonzalez-Alegre, Pedro, Hunter, Nina, McDonald, Craig, Morris, Carl, Tobolowsky, Mark, Wagner, Kathryn R, Ziolkowski, Olivia, and Duan, Dongsheng
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Regenerative Medicine ,Clinical Trials and Supportive Activities ,Biotechnology ,Intellectual and Developmental Disabilities (IDD) ,Gene Therapy ,Orphan Drug ,Duchenne/ Becker Muscular Dystrophy ,Pediatric ,Brain Disorders ,Muscular Dystrophy ,Rare Diseases ,Genetics ,Clinical Research ,5.2 Cellular and gene therapies ,Development of treatments and therapeutic interventions ,Musculoskeletal ,Male ,Humans ,Muscular Dystrophy ,Duchenne ,Muscle ,Skeletal ,Genetic Therapy ,Gene Transfer Techniques ,Biomarkers ,microdystrophin ,Duchenne muscular dystrophy ,gene therapy ,AAV vector ,Clinical Sciences ,Medical biotechnology - Abstract
Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It is caused by mutations in the DMD gene and is characterized by progressive muscle degeneration that results in loss of function and early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets of the patient population, DMD remains a disease with large unmet medical needs. The adeno-associated virus (AAV) vector is the leading gene delivery system for addressing genetic neuromuscular diseases. Since the gene encoding the full-length dystrophin protein exceeds the packaging capacity of a single AAV vector, gene replacement therapy based on AAV-delivery of shortened, yet, functional microdystrophin genes has emerged as a promising treatment. This article seeks to explain the rationale for use of the accelerated approval pathway to advance AAV microdystrophin gene therapy for DMD. Specifically, we provide support for the use of microdystrophin expression as a surrogate endpoint that could be used in clinical trials to support accelerated approval.
- Published
- 2023