[Treatment of Pompe's disease with recombinant enzymes]

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.