Figure 3.

Ivacaftor restores G551D-cystic fibrosis transmembrane conductance regulator (CFTR) function in human bronchial epithelial (HBE) primary cell cultures. a) CFTR activity was evaluated by measuring CFTR-dependent chloride transport (short-circuit current in voltage-clamp mode) relative to wild-type (n=16). Ivacaftor increased the activity of G551D/F508del-CFTR to ∼50% of wild-type (personal communication; F. van Goor, Vertex Pharmaceuticals Inc., Cambridge, MA, USA). Modified from [54]. b) Mean ciliary beat frequency (CBF) after 5 days of treatment with dimethyl sulfoxide (DMSO), 30 nM vasoactive intestinal peptide (VIP) (a naturally occuring CFTR activator), 10 μM ivacaftor (IVA), or 30 nM VIP+10 μM IVA (±sem; n=6). Taken together, the results show that IVA (either alone or in combination with VIP) caused a significant increase in CBF with respect to vehicle control (DMSO). Modified from [52]. *: p<0.05, significant difference between DMSO and G551D/F508del-HBE; ^#: p<0.05, significant difference between DMSO and IVA alone. c) Representative confocal microscopy image of G551D/F508del-HBE cultures treated with vehicle control or ivacaftor. The results show a clear ivacaftor-dependent increase in the depth of airway surface liquid (ASL) relative to control (personal communication; F. van Goor, Vertex Pharmaceuticals Inc., Cambridge, MA, USA). Modified from [52]. d) Dose–response curve of the change in ASL volume in G551D/F508del-HBE after application of ivacaftor at the indicated concentrations (n=3–9). Reproduced from [52].