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

KR Wagner, S Hamed, DW Hadley… - Annals of Neurology …, 2001 - Wiley Online Library
KR Wagner, S Hamed, DW Hadley, AL Gropman, AH Burstein, DM Escolar, EP Hoffman
Annals of Neurology: Official Journal of the American Neurological …, 2001Wiley Online Library
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 …
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.
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