Figure 1.

Early treatment with VX-770 prevents pathological changes in a cystic fibrosis animal model. (A) Effect of the CFTR potentiator VX-770 (ivacaftor) on ion channel gating of the CFTR G551D mutation. The G551D mutation abolishes ATP-dependent gating, which results in reduced channel open probability, but treatment with VX-770 alters activity of the mutant CFTR, leading to greater chloride ion and bicarbonate ion secretion, reduced sodium ion absorption, and hydration of epithelial surfaces. (B) Effect of prenatal and postnatal treatment with VX-770 (ivacaftor) on the airways of young ferrets with G551D mutation. Mucus accumulation, bacterial infection, and endobronchitis develop early in untreated airways of young kits with G551D mutations, but treated animals avoided bronchial infection and inflammation until the drug was discontinued. Similar effects were seen in other affected organs, including the pancreas, intestines, and genitourinary tract. Modified from Ferkol (65).