Rat heart perfusion as model system for enzyme replacement therapy in glycogenosis type II.

Cardiac failure and skeletal muscle weakness are the main clinical features of glycogenosis type II, a lysosomal storage disorder caused by acid alpha-glucosidase deficiency. In our study, we have investigated in a rat heart perfusion-recirculation system whether acid alpha-glucosidase can be taken up from the vascular system into cardiomyocytes. When rat hearts were perfused with mannose 6-phosphate-containing acid alpha-glucosidase purified from bovine testis, a 3- to 4-fold increase of enzyme activity was obtained. Perfusion with human placental acid alpha-glucosidase not containing the mannose 6-phosphate recognition marker did not have such an effect. The presence of bovine testis acid alpha-glucosidase in heart tissue was demonstrated by immunoblotting. Immunocytochemistry provides evidence for uptake of the exogenous enzyme in lysosomes of the cardiomyocytes. The relevance of these findings for enzyme therapy in glycogenosis type II is discussed.