Mutation-specific dual potentiators maximize rescue of CFTR gating mutants.

ABSTRACT:

Background

The potentiator ivacaftor (VX-770) has been approved for therapy of 38 cystic fibrosis (CF) mutations (∼10% of the patient population) associated with a gating defect of the CF transmembrane conductance regulator (CFTR). Despite the success of VX-770 treatment of patients carrying at least one allele of the most common gating mutation G551D-CFTR, some lung function decline and P. aeruginosa colonization persist. This study aims at identifying potentiator combinations that can considerably enhance the limited channel activity of a panel of CFTR gating mutants over monotherapy.

Methods

The functional response of 13 CFTR mutants to single potentiators or systematic potentiator combinations was determined in the human bronchial epithelial cell line CFBE41o- and a subs

SUBMITTER: Veit G 

PROVIDER: S-EPMC7190413 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature