Safety Study of Mini-dystrophin Gene to Treat Duchenne Muscular Dystrophy

The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).

This phase I randomized double blind dose escalation study investigates the safety and efficacy of the mini-dystrophin gene transferred to the biceps muscle for Duchenne muscular dystrophy patients, ages 5 to 12 years of age, using a recombinant adeno-associated virus. Eligible participants must have a known dystrophin gene mutation and may be concurrently treated with corticoid steroids. The mini-dystrophin gene or a placebo agent (normal saline or empty viral capsids) are injected directly into both biceps muscles while under conscious sedation. Following the gene transfer, patients are admitted to the hospital for 48 hours of observation followed by weekly outpatient visits at the Columbus Children's Hospital Neuromuscular Clinic. A bilateral muscle biopsy is preformed following 6 weeks with long term follow up will consisting of bi-annual visits for the next 2 years.

Recombinant adeno-associated virus (AAV) carrying a truncated human dystrophin gene (mini-dystrophin) expressed from a cytomegalovirus (CMV) promoter.

Physical Exams assessing major organ systems and safety labs (GGT, Bilirubin, Glucose, Amylase, CBC/Diff, AFP, Platelets, PT/PTT, Creatinine, Electrolytes, Total protein, Alkaline phosphatase, and Urinalysis)

Inclusion Criteria: Known null mutation of the Dystrophin gene Male age of 5 years or older If taking corticosteroids, must have dose unchanged for the past 3 months Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital) Progressive, symmetrical proximal muscle weakness of arms and legs Exclusion Criteria: Unable to cooperate for muscle strength testing Joint contractures that prohibit muscle strength testing Concomitant illness Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension) Controlled substance abuse

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