Rescue of functional delF508‐CFTR channels in cystic fibrosis epithelial cells by the α‐glucosidase inhibitor miglustat

作者：Caroline Norez, Sabrina Noël, Martina Wilke, Marcel J. C. Bijvelds, Huub Jorna, Patricia Melín, Hugo deJonge, Frédéric Becq · 发表于：FEBS Letters · 年份：2006 · DOI：10.1016/j.febslet.2006.03.010 · 被引用次数：135 · 研究领域：Cystic Fibrosis Research Advances、Lysosomal Storage Disorders Research、Cellular transport and secretion

In the disease cystic fibrosis (CF), the most common mutation delF508 results in endoplasmic reticulum retention of misfolded CF gene proteins (CFTR). We show that the alpha-1,2-glucosidase inhibitor miglustat (N-butyldeoxynojirimycin, NB-DNJ) prevents delF508-CFTR/calnexin interaction and restores cAMP-activated chloride current in epithelial CF cells. Moreover, miglustat rescues a mature and functional delF508-CFTR in the intestinal crypts of ileal mucosa from delF508 mice. Since miglustat is an orally active orphan drug (Zavesca) prescribed for the treatment of Gaucher disease, our findings provide the basis for future clinical evaluation of miglustat in CF patients.