Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part I: rationale.

摘要

Since the identification of abnormalities in the dystrophin gene as primary cause of Duchenne muscular dystrophy, gene therapy has been seen as an obvious option among various approaches to treat the disease. It is also considered to be especially challenging, as in this context, one must achieve massive transfer of the gene with a sustained lifelong correction of the muscle phenotype.Our goal is to allow large scale transfection of skeletal muscle fibers of Duchenne muscular dystrophy patients with the full-length 11-kb human dystrophin cDNA. Extensive in vitro and in vivo studies, together with safety considerations and the prospects of a very efficient intra-arterial delivery procedure, led us progressively to focus our efforts on plasmid DNA administration. We are now conducting a phase I safety clinical trial which will pave the way for future therapeutic gene therapy trials for Duchenne muscular dystrophy.