Pharmacological rescue of the G85E CFTR variant by preclinical and approved modulators.

ABSTRACT:

Introduction

Cystic Fibrosis (CF) is a genetic disease due to loss-of-function mutations of the CFTR channel. F508del is the most frequent mutation (70% of alleles in Italy), while other mutations have much lower frequency. Among them, G85E (0.4% frequency globally, 1.13% in Italy) emerges as a mutation characterized by a severe CFTR folding and trafficking defect.

Methods

To investigate the pharmacological responsiveness of the G85E-CFTR variant, we performed a functional and biochemical characterization in heterologous expression systems and ex vivo models based on patient-derived human nasal epithelial cells (HNEC).

Results

Our study demonstrated that treatment of primary airway cells with elexacaftor and tezacaftor causes a significant (although modest) res

SUBMITTER: Tomati V 

PROVIDER: S-EPMC11608983 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature