title: Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations.
abstract: Aminoglycosides have previously been shown to suppress nonsense mutations, allowing translation of full-length proteins in vitro and in animal models. In the mdx mouse, where muscular dystrophy is due to a nonsense mutation in the dystrophin gene, gentamicin suppressed truncation of the protein and ameliorated the phenotype. A subset of patients with Duchenne and Becker muscular dystrophy similarly possess a nonsense mutation, causing premature termination of dystrophin translation. Four such patients, with various stop codon sequences, were treated once daily with intravenous gentamicin at 7.5 mg/kg/day for 2 weeks. No ototoxicity or nephrotoxicity was detected. Full-length dystrophin was not detected in pre- and post-treatment muscle biopsies.
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. kwagner@mail.jhmi.edu
authors.forename: K R
authors.initials: KR
authors.lastname: Wagner
authors.forename: S
authors.initials: S
authors.lastname: Hamed
authors.forename: D W
authors.initials: DW
authors.lastname: Hadley
authors.forename: A L
authors.initials: AL
authors.lastname: Gropman
authors.forename: A H
authors.initials: AH
authors.lastname: Burstein
authors.forename: D M
authors.initials: DM
authors.lastname: Escolar
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: K H
authors.initials: KH
authors.lastname: Fischbeck
mesh_terms: D000293:Adolescent; D001706:Biopsy; D015153:Blotting, Western; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D016189:Dystrophin / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: D018389:Codon, Nonsense; D016189:Dystrophin; D005839:Gentamicins; D003402:Creatine Kinase