Report of the MDA Gene Therapy Conference, Tucson, Arizona, September 27-28, 1991.

Abstract

C. Thomas Caskey, in summarizing the meeting, noted that phenotypic correction of DMD is likely to require restoration of the dystrophin protein; thus, this disease is a logical target for consideration of gene replacement therapy. A number of tools are available to the experimenter, including the dystrophin gene and cDNA, several viral vectors, and various animal models of the human disease. In addition, detailed knowledge is now becoming available about the mechanisms of muscle-specific gene expression. However, a number of uncertainties have yet to be resolved. The dystrophin gene has an extremely complex pattern of expression, with more than one promoter and a number of alternative splicing events; what are the reasons for this variety? The dystrophin-glycoprotein complex has been described but its function is unclear. The role of the satellite cell is uncertain. It is not yet clear whether viral delivery or direct injection of DNA will be the method of choice for gene transfer into muscle. If delivery methods do not target the appropriate tissues, then appropriate use of tissue-specific control elements will be required for selective gene expression. Which animal model system should be used? What role can myoblast transplantation (with or without gene transfer) play in the treatment of DMD and other inherited myopathies? It is hoped that in further meetings on this topic, some of these issues will have been resolved.