Research ArticleCystic Fibrosis

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

Science Translational Medicine  23 Jul 2014:
Vol. 6, Issue 246, pp. 246ra97
DOI: 10.1126/scitranslmed.3008889

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Potentiating Trouble

Cystic fibrosis is a genetic disease caused by mutations of the CFTR ion channel, resulting in pulmonary and other complications. Ivacaftor is the only targeted drug approved for cystic fibrosis, but it is not effective enough to treat the severest and most common form of this disease. Ivacaftor is a “potentiator,” which means that it improves the activity of mutant CFTR, but cannot work if there is no CFTR on the cell surface. Other drugs, called “correctors,” help bring mutant CFTR to the cell surface, but two manuscripts by Cholon and Veit and co-authors now show that combining the two types of drugs does not work effectively because potentiators make CFTR less stable, accelerating the removal of this channel from the cell membrane.