Gene therapy for muscular dystrophy: current progress and future prospects.
Muscular dystrophies refer to a group of inherited disorders characterized by progressive muscle weakness, wasting and degeneration. So far, there is no effective treatment but new gene-based therapies are currently being developed with particular noted advances in using conventional gene replacement strategies, RNA-based approaches, or cell-based gene therapy with a main focus on Duchenne muscular dystrophy (DMD). DMD is the most common and severe form of muscular dystrophy and current treatments are far from adequate. However, genetic and cell-based therapies, in particular exon skipping induced by antisense strategies, and corrective gene therapy via functionally engineered dystrophin genes hold great promise, with several clinical trials ongoing. Proof-of-concept of exon skipping has been obtained in animal models, and most recently in clinical trials; this approach represents a promising therapy for a subset of patients. In addition, gene-delivery-based strategies exist both for antisense-induced reading frame restoration, and for highly efficient delivery of functional dystrophin mini- and micro-genes to muscle fibres in vivo and muscle stem cells ex-vivo. In particular, AAV-based vectors show efficient systemic gene delivery to skeletal muscle directly in vivo, and lentivirus-based vectors show promise of combining ex vivo gene modification strategies with cell-mediated therapies.
Trollet
Capucine
C
School of Biological Sciences, Royal Holloway-University of London, Egham, TW20 0EX, Surrey, UK.
Athanasopoulos
Takis
T
Popplewell
Linda
L
Malerba
Alberto
A
Dickson
George
G
D000818:Animals; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends*; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D055435:Myostatin / Q000037:antagonists & inhibitors; D012313:RNA / Q000235:genetics; D012342:RNA, Small Nuclear / Q000627:therapeutic use
D055435:Myostatin; D012342:RNA, Small Nuclear; D012313:RNA