Pompe disease is a lysosomal storage disorder that is characterized by a
deficiency in the acid alpha-glucosidase enzyme that is responsible for the
breakdown of glycogen to glucose. The lack of degradation results in the accumulation
of glycogen in lysosomes, predominantly affecting cardiac and skeletal
muscles. In cases of complete enzyme deficit, such as observed in the infantile
manifestation, cardiomyopathy, and skeletal muscle myopathy occur with fatal
consequences. As with other lysosomal storage disorders, enzyme replacement
therapy (ERT) is the patient’s only hope. Alglucosidase alfa has been developed and launched as the ERT for Pompe disease. As a recombinant human enzyme, it
is produced by transfected CHO cells as a 110-kDa precursor that targets
lysosomes via the mannose-6-phosphate (M6P) receptor. Following endocytosis,
the enzyme is transformed to its mature 76-kDa form that restores glycogen
processing and reverses accumulation. The dosing regimen of alglucosidase
alfa is 20 mg/kg infused over a period of 4 h every two weeks. The pharmacokinetic
properties are dose-proportional between 20 and 40mg/kg.
