This article is a US Government work and, as such, is in the public domain of the United States of America.
Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations †
Version of Record online: 3 APR 2001
Published 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 49, Issue 6, pages 706–711, June 2001
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
- Issue online: 5 JUN 2001
- Version of Record online: 3 APR 2001
- Manuscript Revised: 5 JAN 2001
- Manuscript Accepted: 5 JAN 2001
- Manuscript Received: 20 OCT 2000
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke. Grant Number: NS29525-09
- Passano Foundation, Physician Scientist Award
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.