January 8, 2009: Published ahead of print Am. J. Respir. Cell Mol. Biol. 2009, doi:10.1165/rcmb.2008-0285OC

A CF respiratory epithelial cell chronically treated by miglustat acquires a non-CF like phenotype
Caroline Norez1, Fabrice Antigny1, Sabrina Noel1, Clarisse
Vandebrouck1, and Frederic Becq1*
1 Institut de Physiologie et Biologie Cellulaires, Universite de
Poitiers, Poitiers, France

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
hyperabsorption by the airways, mediated by the epithelial Na+
channel (ENaC), profound lung inflammation and dysregulation of the
calcium homeostasis are presumably causally related to loss of CFTR-
dependent chloride function in CF patients. Miglustat (N-
butyldeoxynojirimycin, Zavesca®), an inhibitor of the -1,2
glucosidase has been proposed for clinical use in CF due to its
effect as corrector of the defective trafficking of F508del-CFTR. In
the present study we show that the daily treatment for 2 months with
low concentration of miglustat on the human CF nasal epithelial cell
line JME/CF15 (F508del/F508del-CFTR) results in progressive, stable,
reversible and sustained correction of F508del-CFTR trafficking, down-
regulation of sodium hyperabsorption and regulation of the calcium
homeostasis. In conclusion, we provided here the first evidence that
a respiratory CF cell can acquire a non-CF like phenotype when
chronically treated with low-concentration of a pharmacological drug.

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