[Molecular basis of treatment in Gaucher's disease]

In Gaucher's disease (GD) there is an imbalance in the monocyte-macrophage system between the rate of formation and degradation of glucosylceramide due to low activity of the lysosomal enzyme betaglucorebrosidase. Therapeutic approaches are aimed to reduce the synthesis of glucosylceramide by inhibiting ceramide-glucosyltransferase or increasing the degradation of glucosylceramide using a recombinant beta-glucorebrosidase or recovering the residual activity of mutant enzymes with pharmacological chaperones. Inhibitory molecules of ceramide-glucosyltransferase used mimic glucose or ceramide. All recombinant enzymes used in GD enzyme replacement therapy have similar kinetic parameters, but differ in their amino acid sequence, as well as, in the exposed mannose oligosaccharide chains. The mannose content and localization in the oligosaccharide chains are essential for cell uptake. Velaglucerase alpha have a high content of mannoses in their oligosaccharide chains.