Receptor-mediated uptake of acid alpha-glucosidase corrects lysosomal glycogen storage in cultured skeletal muscle.

Attempts at treatment of glycogenosis type II and other lysosomal storage disorders by enzyme replacement have been reported. Parenteral enzyme administration has been ineffectual. Treatment by bone marrow transplantation is currently under investigation. We have used cultured skeletal muscle cells from a patient with infantile glycogenosis type II to study fundamental aspects of enzyme replacement therapy. Efficient uptake of acid alpha-glucosidase was achieved by using the mannose-6-phosphate receptor on the cell surface as a target for an enzyme precursor with phosphorylated high-mannose types carbohydrate chains purified from human urine. We found that the enzyme was channeled to the lysosomes and converted to mature acid alpha-glucosidase. Glycogen storage was reversed. The results are discussed in relation to treatment of glycogenosis type II.