earticle

영어

Patients with Fabry disease have a defect in the gene for the lysosomal enzyme α- galactosidase A (α-GAL). This defect results in an inability or diminished ability to catabolize lipids with terminal α-galactosyl residues. In the absence of lysosomal enzyme α-galactosidase A, these lipids, particularly globotriaosylceramide (GL-3), accumulate progressively in the lysosomes of many cell types throughout the body. GL-3 accumulation in renal endothelial cells may play a role in renal failure. Enzyme-replacement therapy (ERT) is an established means of treating lysosomal storage diseases such as Fabry disease. Infused therapeutic enzymes are targeted to lysosomes of affected cells by interactions with cell-surface receptors that recognize carbohydrate moieties, such as mannose and mannose 6-phosphate, on the enzymes. Production of effective mannose-6-phosphate-targeted ERTs for some disorders is difficult, because lysosomal enzymes have a short half-life when injected into the bloodstream because of rapid clearance in the liver by other carbohydrate-recognizing receptors, particularly the mannose receptor that is highly abundant on Kupffer cells. In this presentation, we can discuss the approach to control carbohydrate moieties to improve the efficacy of therapeutic enzyme.