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.
Pari
G
G
Neuromuscular Research Group, Montreal Neurological Institute, McGill University, Quebec, Canada.
Crerar
M M
MM
Nalbantoglu
J
J
Shoubridge
E
E
Jani
A
A
Tsujino
S
S
Shanske
S
S
DiMauro
S
S
Howell
J M
JM
Karpati
G
G
D000818:Animals; D018014:Gene Transfer Techniques; D006012:Glycogen Storage Disease Type V / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D006005:Phosphorylases / Q000235:genetics*; D012756:Sheep
D006005:Phosphorylases