*7.4. Potentiation with Ivacaftor*

UDCA and 4-PB have been shown to correct the misfolding of trafficking-deficient variants. However, several disease-associated mutations (especially those in the NBDs) do not interfere with folding, trafficking and canalicular localization, but rather lead to impairment of transporter function [65,119]. Ivacaftor (VX-770) a potentiator has been approved by the FDA for treatment of some class III (gating deficient) CFTR mutants [136,137]. In these variants, an improvement of respiratory function could be demonstrated. Similar to clinical results in CFTR patients, ivacaftor was shown to rescue the function of missense mutations in the NBDs of ABCB4/MDR3 [138]. Recently, Mareux and co-workers showed that ivacaftor also rescued the function of an NBD missense mutation (T463I) of BSEP [110]. The mechanism of action of ivacaftor presently remains unclear.
