T.P.14 Gentamicin treatment of nonsense-mediated Duchenne Muscular Dystrophy: A case report

Abstract

About 13% of patients Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene leading to premature stop codon. Aminoglycoside-induced ribosomal readthrough of premature stop codons has been shown to restore dystrophin to skeletal muscles in mdx mice. In clinical trials gentamicin use was associated with decreased serum levels and increased dystrophin expression on muscle biopsies. To report the clinical outcome of 3.3year of IV gentamicin therapy in a patient with DMD. Subject is a 21year old patient who was diagnosed with DMD at age 7 with muscle biopsy showing non-reactive staining to 3 dys antibodies and a small group of revertant fibers; and has a nonsense mutation in exon 59 of the dystrophin gene. Independent ambulation was lost at age 11.5 after bilateral heel cord releases and scoliosis surgery for a 110 degree curve was done at age 15.5years. Glucocorticoids (daily deflazacort 30mg) were started at age 15.8year. with improved upper extremity strength and pulmonary function. Intravenous gentamicin 7.5mg/kg/week was started from age 17.2years with a concomitant decreased deflazacort dose to 30mg every other day (qod). Subject showed increased motor and pulmonary function at 6months after starting IV Gentamicin therapy and deflazacort was further decreased to 15mg qod. Decline in muscle strength and pulmonary function was noted at 20months of IV gentamicin and with decreased deflazacort dose. Mildly Improved PFT was noted after increasing deflazacort to daily 15mg at at 18.5year. Subject is overall doing well with quite stable pulmonary and motor function at age 21year with no ototoxicity or renal toxicity for the past 3.3year. This case highlights the clinical benefit of 3.3year of weekly IV gentamicin and low dose daily deflazacort therapy in a subject with nonsense-mediated DMD without significant adverse effects.