INTRAVENOUS GENTAMICIN IN DUCHENNE MUSCULAR DYSTROPHY

Ohio State University, Columbus OH

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Linked publications & trials

Abstract

We propose to evaluate the efficacy and safety of intravenous gentamicin therapy in Duchenne muscular dystrophy (DMD) and limb girdle muscular dystrophy (LGMD) patients with point mutations. The primary objective of this study is to assess the efficacy of the drug on promoting gene expression of full-length dystrophin, the protein that is deficient in DMD, or calpain, dysferlin, caveolin and sarcoglycans, the proteins that may be deficient in LGMD. For this purpose we are planning to treat 10 patients with proven diagnosis of DMD or LGMD and nonsense point mutations with intravenous gentamicin, dose 7.5mg/kg/day, over 14 days. This will be done in an open manner. A muscle biopsy performed before and after the treatment will assess the main aim of the study. Different clinical tests to assess muscle strength and function will be done just before and immediately after the treatment and then every 2 weeks for a period of 4 weeks. Hearing and kidney function will be closely monitored during the treatment, for safety reasons. This trial is based on the recently reported capability of gentamicin to misread the stop codon in the mdx mouse promoting expression of full-length dystrophin. DMD and LGMD do not have definitive treatment. If this study is successful, it will represent a new therapeutic approach for these patients and it may open a new strategy for other human diseases caused by point mutations leading to stop codons.