Myophosphorylase gene transfer in McArdle's disease myoblasts in vitro.

McArdle's disease is due to a genetic deficiency of glycogen phosphorylase and results in a lack of glucose mobilization from glycogen during anaerobic exercise. A genetic defect in Merino sheep produces a similar picture. We constructed a first-generation adenoviral recombinant containing the full-length human phosphorylase cDNA under the control of the Rous sarcoma virus promoter. Primary myoblast cultures from phosphorylase-deficient human and sheep muscle were efficiently transduced with this vector, resulting in restoration of the phosphorylase activity. A similar correction of the genetic defect in muscles of McArdle's patients in vivo appears feasible, preferably with the use of an adeno-associated viral vector.