Original Article
Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function,☆☆

https://doi.org/10.1016/j.jcf.2013.06.008Get rights and content
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Abstract

Background

Ivacaftor (KALYDECO™, VX-770) is a CFTR potentiator that increased CFTR channel activity and improved lung function in patients age 6 years and older with CF who have the G551D-CFTR gating mutation. The aim of this in vitro study was to evaluate the effect of ivacaftor on mutant CFTR protein forms with defects in protein processing and/or channel function.

Methods

The effect of ivacaftor on CFTR function was tested in electrophysiological studies using a panel of Fischer rat thyroid (FRT) cells expressing 54 missense CFTR mutations that cause defects in the amount or function of CFTR at the cell surface.

Results

Ivacaftor potentiated multiple mutant CFTR protein forms that produce functional CFTR at the cell surface. These included mutant CFTR forms with mild defects in CFTR processing or mild defects in CFTR channel conductance.

Conclusions

These in vitro data indicated that ivacaftor is a broad acting CFTR potentiator and could be used to help stratify patients with CF who have different CFTR genotypes for studies investigating the potential clinical benefit of ivacaftor.

Keywords

CFTR
Ivacaftor
Potentiator
VX-770

Cited by (0)

This study is sponsored by Vertex Pharmaceuticals Incorporated.

☆☆

F. Van Goor, H. Yu, B. Burton, and B.J. Hoffman are employees of Vertex Pharmaceuticals Inc. and may own stock or options in that company.