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J Cyst Fibros. 2018 Mar;17(2S):S22-S27. doi: 10.1016/j.jcf.2017.10.006. Epub 2017 Nov 6.

Ion channels as targets to treat cystic fibrosis lung disease.

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School of Pharmacy, Queen's University Belfast, Northern Ireland, UK. Electronic address:
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA.
Department of Medical Biochemistry, Semmelweis University, Budapest 1094, Hungary.


Lung health relies on effective mucociliary clearance and innate immune defence mechanisms. In cystic fibrosis (CF), an imbalance in ion transport due to an absence of chloride ion secretion, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and a concomitant sodium hyperabsorption, caused by dyregulation of the epithelial sodium channel (ENaC), results in mucus stasis which predisposes the lungs to cycles of chronic infection and inflammation leading to lung function decline. An increased understanding of CFTR structure and function has provided opportunity for the development of a number of novel modulators targeting mutant CFTR however, it is important to also consider other ion channels and transporters present in the airways as putative targets for drug development. In this review, we discuss recent advances in CFTR biology which will contribute to further drug discovery in the field. We also examine developments to inhibit the epithelial sodium channel (ENaC) and potentially activate alternative chloride channels and transporters as a multi-tracked strategy to hydrate CF airways and restore normal mucociliary clearance mechanisms in a manner independent of CFTR mutation.


Airways hydration; Anion exchanger; CFTR; Cystic fibrosis; ENaC; Ion channel; Ion transporter; Proteases

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