title: Drug Discovery of Therapies for Duchenne Muscular Dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by the loss of the muscle protein, dystrophin, leading to progressive loss of muscle fibers and muscle weakness. Drug discovery efforts targeting DMD have used two main approaches: (1) the restoration of dystrophin expression or the expression of a compensatory protein, and (2) the mitigation of downstream pathological mechanisms, including dysregulated calcium homeostasis, oxidative stress, inflammation, fibrosis, and muscle ischemia. The aim of this review is to introduce the disease, its pathophysiology, and the available research tools to a drug discovery audience. This review will also detail the most promising therapies that are currently being tested in clinical trials or in advanced preclinical models.
authors.affiliation: Wynnewood, PA, USA yblat1@comcast.net.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Blat
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Shachar
authors.initials: S
authors.lastname: Blat
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001583:Benzoxazoles / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D055808:Drug Discovery; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000503:physiopathology; D010069:Oxadiazoles / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D001583:Benzoxazoles; D016189:Dystrophin; D010069:Oxadiazoles; C000610115:SMT C1100; C515878:ataluren; D002118:Calcium
keywords: Duchenne muscular dystrophy; dystrophin; review; skeletal muscle