Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations

Ann Neurol. 2001 Jun;49(6):706-11.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Biopsy
  • Blotting, Western
  • Child
  • Codon, Nonsense / genetics*
  • Creatine Kinase / blood
  • Dystrophin / biosynthesis
  • Dystrophin / chemistry
  • Dystrophin / genetics
  • Dystrophin / immunology
  • Gentamicins / administration & dosage
  • Gentamicins / adverse effects
  • Gentamicins / therapeutic use*
  • Humans
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Duchenne / blood
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism
  • Phenotype
  • Treatment Outcome

Substances

  • Codon, Nonsense
  • Dystrophin
  • Gentamicins
  • Creatine Kinase