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

Kathryn R. Wagner, Sherifa Hamed, Donald W. Hadley, Andrea L. Gropman, Aaron H. Burstein, Diana M. Escolar, Eric P. Hoffman, Kenneth H. Fischbeck

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)706-711
Number of pages6
JournalAnnals of neurology
Volume49
Issue number6
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Wagner, K. R., Hamed, S., Hadley, D. W., Gropman, A. L., Burstein, A. H., Escolar, D. M., Hoffman, E. P., & Fischbeck, K. H. (2001). Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. Annals of neurology, 49(6), 706-711. https://doi.org/10.1002/ana.1023