CHEMICAL CHAPERONE THERAPY FOR GAUCHER DISEASE: N-OCTYL-BETA-VALIENAMINE INCREASES THE CELLULAR ACTIVITY OF NOT ONLY F213I BUT ALSO N188S BETAGLUCOCEREBROSIDASES

Abstract

Objectives: Chemical chaperone therapy is a novel therapeutic strategy for glycolipid storage disorders to stabilize and accelerate transport of mutant enzymes by using a low molecular chemical that mimics a carbohydrate and inhibits the enzyme activity in vitro. We reported a carbohydrate mimic N-octyl-beta-valienamine (NOV) up-regulated cellular enzyme activity of Gaucher disease fibroblasts with a F213I beta-Glc mutation (2004). We have screened whether NOV works as a chemical chaperone for other beta-Glc mutant forms.