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

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 i n the dystrophin gene, gentamicin suppressed truncation of the protein and ameliorated the phenotype. A subset of patients with Duchenne and Becker mu scular dystrophy similarly possess a nonsense mutation, causing premature t ermination 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. Ful l-length dystrophin was not detected in pre- and post-treatment muscle biop sies.