Original Article

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

  1. Kathryn R. Wagner MD, PhD1,2,*,
  2. Sherifa Hamed MD3,
  3. Donald W. Hadley MS1,4,
  4. Andrea L. Gropman MD1,
  5. Aaron H. Burstein PharmD5,
  6. Diana M. Escolar MD3,6,
  7. Eric P. Hoffman PhD3,
  8. Kenneth H. Fischbeck MD1

Article first published online: 3 APR 2001

DOI: 10.1002/ana.1023

Issue

Annals of Neurology

Annals of Neurology

Volume 49, Issue 6, pages 706–711, June 2001

Additional Information

How to Cite

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

Author Information

  1. 1

    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD

  2. 2

    Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD

  3. 3

    Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC

  4. 4

    Medical Genetics Branch/National Human Genome Research Institute, National Institutes of Health, Bethesda, MD

  5. 5

    Clinical Pharmacokinetics Research Laboratory, National Institutes of Health, Bethesda, MD

  6. 6

    Department of Neurology, George Washington University, Washington, DC

*Department of Neurology, The Johns Hopkins Hospital, 607 PCTB, 725 North Wolfe Street, Baltimore, MD 21205

  1. †

    This article is a US Government work and, as such, is in the public domain of the United States of America.

Publication History

  1. Issue published online: 5 JUN 2001
  2. Article first published online: 3 APR 2001
  3. Manuscript Revised: 5 JAN 2001
  4. Manuscript Accepted: 5 JAN 2001
  5. Manuscript Received: 20 OCT 2000

Funded by

  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke. Grant Number: NS29525-09
  • Passano Foundation, Physician Scientist Award

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (416K)

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.

View Full Article (HTML) Get PDF (416K)