title: The Pathogenesis and Therapy of Muscular Dystrophies.
abstract: Current molecular genomic approaches to human genetic disorders have led to an explosion in the identification of the genes and their encoded proteins responsible for these disorders. The identification of the gene altered by mutations in Duchenne and Becker muscular dystrophy was one of the earliest examples of this paradigm. The nearly 30 years of research partly outlined here exemplifies the road that similar current gene discovery protocols will be expected to travel, albeit much more rapidly owing to improved diagnosis of genetic disorders and an understanding of the spectrum of mutations thought to cause them. The identification of the protein dystrophin has led to a new understanding of the muscle cell membrane and the proteins involved in membrane stability, as well as new candidate genes for additional forms of muscular dystrophy. Animal models identified with naturally occurring mutations and developed by genetic manipulation have furthered the understanding of disease progression and underlying pathology. The biochemistry and molecular analysis of patient samples have led to the different dystrophin-dependent and -independent therapies that are currently close to or in human clinical trials. The lessons learned from decades of research on dystrophin have benefited the field of human genetics.
authors.affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, OX1 3PT Oxford, United Kingdom; email: simon.guiraud@dpag.ox.ac.uk , kay.davies@dpag.ox.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Guiraud
authors.forename: Annemieke
authors.initials: A
authors.lastname: Aartsma-Rus
authors.forename: Natassia M
authors.initials: NM
authors.lastname: Vieira
authors.forename: Kay E
authors.initials: KE
authors.lastname: Davies
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Louis M
authors.initials: LM
authors.lastname: Kunkel
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009136:Muscular Dystrophies / Q000503:physiopathology* / Q000628:therapy*; D009154:Mutation; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D013256:Steroids / Q000627:therapeutic use; D049411:Utrophin / Q000235:genetics / Q000378:metabolism
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D013256:Steroids; C483599:UTRN protein, human; D049411:Utrophin; D010727:Phosphoric Diester Hydrolases
keywords: DMD; clinical trials; muscle; muscular dystrophy; therapy