Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139, USA.
J Cyst Fibros. 2012 May;11(3):237-45. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30.
The investigational CFTR potentiator ivacaftor (VX-770) increased CFTR channel activity and improved lung function in subjects with CF who have the G551D CFTR gating mutation. The aim of this in vitro study was to determine whether ivacaftor potentiates mutant CFTR with gating defects caused by other CFTR gating mutations.
The effects of ivacaftor on CFTR channel open probability and chloride transport were tested in electrophysiological studies using Fischer rat thyroid (FRT) cells expressing different CFTR gating mutations.
Ivacaftor potentiated multiple mutant CFTR forms with defects in CFTR channel gating. These included the G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P and G1349D CFTR gating mutations.
These in vitro data suggest that ivacaftor has a similar effect on all CFTR forms with gating defects and support investigation of the potential clinical benefit of ivacaftor in CF patients who have CFTR gating mutations beyond G551D.
在患有 CFTR 门控突变 G551D 的 CF 患者中，研究性 CFTR 增效剂 ivacaftor（VX-770）可增加 CFTR 通道活性并改善肺功能。本体外研究旨在确定 ivacaftor 是否可增强由其他 CFTR 门控突变引起的门控缺陷的突变型 CFTR。
使用表达不同 CFTR 门控突变的 Fischer 大鼠甲状腺（FRT）细胞进行电生理学研究，检测 ivacaftor 对 CFTR 通道开放概率和氯离子转运的影响。
ivacaftor 可增强多种具有 CFTR 通道门控缺陷的突变型 CFTR 形式。这些突变包括 G551D、G178R、S549N、S549R、G551S、G970R、G1244E、S1251N、S1255P 和 G1349D CFTR 门控突变。
这些体外数据表明，ivacaftor 对所有具有门控缺陷的 CFTR 形式均具有相似的作用，并支持在除 G551D 以外的 CFTR 门控突变的 CF 患者中研究 ivacaftor 的潜在临床益处。
