Twenty years after discovering the cystic fibrosis gene, new therapies that treat the underlying defect are coming to fruition. Recent advances in our understanding of the effect of cystic fibrosis transmembrane conductance regulator (CFTR) mutations on the ion channel function of the protein have enabled the discovery of small molecules that restore absent or dysfunctional CFTR activity. Ivacaftor is a CFTR potentiator that improves chloride transport by enhancing channel gating (conformational change between opening and closing states of a channel), and is particularly effective in restoring the activity of G551D-CFTR. In phase III clinical trials, ivacaftor was associated with marked improvements in the clinical status of cystic fibrosis (CF) patients with G551D-CFTR mutations, including improvements in pulmonary function and frequency of exacerbations, in addition to improved quality of life and weight gain. Ivacaftor has also demonstrated activity in other CFTR mutations, including patients with F508del-CFTR co-treated with CFTR folding correctors (e.g., VX-809). As such, ivacaftor represents a major advance in CF therapeutics, opening a new era of mutation-specific therapy to treat the disease. Copyright © 2012 Prous Science, S.A.U. or its licensors. All rights reserved.
