A cystic fibrosis respiratory epithelial cell chronically treated by miglustat acquires a non-cystic fibrosislike phenotype

Cystic fibrosis (CF) is a fatal, autosomal and recessive genetic disease that is mainly due to inactivating mutations in the chloride channel CF transmembrane conductance regulator (CFTR). Sodium hyper-absorption by the airways, profound lung inflammation, and dysre-gulation of calcium homeostasis, are presumably causally related to loss of CFTR-dependent chloride function in patients with CF. Miglustat (N-butyldeoxynojirimycin, Zavesca), an inhibitor of the a-1,2 glucosidase, has been proposed for clinical use in CF because of its effect as a corrector of the defective trafficking of F508del-CFTR. In the present study, we show that daily treatment for 2 months with low concentrations of miglustat on the human CF nasal epithelial cell line, JME/CF15 (F508del/F508del-CFTR), results in progressive, sta-ble, reversible, and sustained correction of F508del-CFTR trafficking, down-regulation of sodium hyperabsorption, and regulation of the calcium homeostasis. In conclusion, we provide here the first evidence that a respiratory CF cell can acquire a non–CF-like pheno-type when chronically treated with low concentrations of a pharma-cological drug