ABSTRACT: The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.
From the Department of Rehabilitation Medicine and Institute for Stem Cell and Regenerative Medicine, University of Washington (RB, DLM, MKC); and Fred Hutchinson Cancer Research Center (ZW), Seattle, Washington.
All correspondence and requests for reprints should be addressed to: Martin K. Childers, DO, PhD, University of Washington, Campus Box 358056, S184, South Research Building, 950 Republican St, Seattle, WA 98109.
Dr. Childers is a paid member of the Scientific Advisory Board for Audentes Therapeutics and holds stock options in the company.
Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.