Pompe disease is caused by the congenital deficiency of the lysosomal enzyme 
acid alpha-glucosidase. The accumulation of lysosomal glycogen results in a 
fatal myopathy and cardiomyopathy. We developed an enzyme replacement therapy 
based on recombinant human acid alpha-glucosidase enzyme targeted to the organs 
of interest by the presence of mannose-6-phosphate on this precursor enzyme and 
a manose-6-phosphate receptor present in muscle and heart. Using molecular 
techniques and following extensive selection, Chinese hamster ovary cells were 
developed that produced very large quantities of precursor human acid 
alpha-glucosidase in the culture medium. An improved method of purification of 
this precursor enzyme from tissue culture medium was developed. This purified 
precursor enzyme was taken up efficiently by patient's fibroblasts, and 
corrected with a single dose the lysosomal glycogen accumulation for one week. 
Finally, intravenous administration of the recombinant enzyme corrected the 
pathology and symptoms of an animal model of this disorder, the acid 
alpha-glucosidase deficient Japanese quail.