Gene therapy research for Duchenne and Becker muscular dystrophies

Abstract

Gene therapy is a promising option for the definitive treatment of Duchenne and Becker muscular dystrophies. Presently, gene therapy for Duchenne and Becker muscular dystrophies is still in the preclinical stage with dystrophin-deficient animals (the mdx mouse and a golden retriever dog strain) serving as convenient models. The thrust of research during the past 18 months has focused on two approaches: adenovirus-mediated dystrophin gene transfer and upregulation of a natural dystrophin analogue, utrophin. In the area of adenovirus-mediated gene transfer, substantial progress has been made in characterizing and mitigating the deleterious immune responses to the vector and transgene proteins. Furthermore, new adenovirus vectors have been created with reduced immunogenicity and increased insert gene capacity, which enhance the longevity of the transgene expression. Additional efforts are underway to develop safe and efficient routes of administration of the adenovirus vector carrying the dystrophin expression cassette. The prospects of utrophin upregulation as an attractive strategy for treatment of Duchenne and Becker muscular dystrophies was greatly enhanced by the demonstration of a substantial mitigation of the dystrophic phenotype of the transgenic mdx mouse overexpressing utrophin.