GENE-THERAPY RESEARCH FOR DUCHENNE AND BECKER MUSCULAR-DYSTROPHIES

Gene therapy is a promising option for the definitive treatment of Duc henne and Becker muscular dystrophies. Presently, gene therapy for Duc henne and Becker muscular dystrophies is still in the preclinical stag e with dystrophin-deficient animals (the mdx mouse and a golden retrie ver dog strain) serving as convenient models. The thrust of research d uring the past 18 months has focused on two approaches: adenovirus-med iated dystrophin gene transfer and upregulation of a natural dystrophi n 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 im munogenicity and increased insert gene capacity, which enhance the lon gevity 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 Duche nne and Becker muscular dystrophies was greatly enhanced by the demons tration of a substantial mitigation of the dystrophic phenotype of the transgenic mdx mouse overexpressing utrophin.