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 α-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.

Calnexin, Castanospermine, Chloride channels, Cystic fibrosis transmembrane conductance regulator, delF508-mice, Miglustat,
F E B S Letters
Department of Biochemistry

Norez, C, Noel, S, Wilke, M, Bijvelds, M.J.C, Jorna, H, Melin, P, … Becq, F. (2006). Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the α-glucosidase inhibitor miglustat. F E B S Letters, 580(8), 2081–2086. doi:10.1016/j.febslet.2006.03.010