Therapeutic strategies for Duchenne and Becker dystrophies.
Duchenne muscular dystrophy (DMD), a severe X-linked genetic disease affecting one in 3500 boys, is the most common myopathy in children. DMD is due to a lack of dystrophin, a submembrane protein of the cytoskeleton, which leads to the progressive degeneration of skeletal, cardiac, and smooth muscle tissue. A milder form of the disease, Becker muscular dystrophy (BMD), is characterized by the presence of a semifunctional truncated dystrophin, or reduced levels of full-length dystrophin. DMD is the focus of three different supportive or therapeutic approaches: gene therapy, cell therapy, and drug therapy. Here we consider these approaches in terms of three potential goals: improvement of dystrophic phenotype, expression of dystrophin, and overexpression of utrophin. Utrophin exhibits 80% homology with dystrophin and is able to perform similar functions. Pharmacological strategies designed to overexpress utrophin appear promising and may circumvent many obstacles to gene and cell-based therapies.
Voisin
Vincent
V
Laboratoire de Neurobiologie Cellulaire et Moléculaire, 91198 Gif sur Yvette, France.
de la Porte
Sabine
S
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000639:trends; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D015316:Genetic Therapy / Q000639:trends; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D049411:Utrophin / Q000235:genetics / Q000378:metabolism
D016189:Dystrophin; D049411:Utrophin; D019001:Nitric Oxide Synthase