Elexacaftor/Tezacaftor/Ivacaftor Accelerates Wound Repair in Cystic Fibrosis Airway Epithelium

Abstract

Background: Cystic fibrosis (CF) airway epithelium shows alterations in repair following damage. In vitro studies showed that lumacaftor/ivacaftor (Orkambi) may favor airway epithelial integrity in CF patients. Our aim was to evaluate the effect of the novel triple combination elexacaftor/tezacaftor/ivacaftor (ETI) on wound repair in CF airway epithelial cells. Methods: A tip-based scratch assay was employed to study wound repair in monolayers of CFBE14o- cells overexpressing the F508del mutation. ETI was added during wound repair. Results: ETI efficiently rescued CFTR F508del maturation and activity, accelerated wound closure and increased wound healing rates of the injured CF cell monolayers. Conclusions: The triple corrector/potentiator combination ETI shows promise in ameliorating wound healing of the airway epithelium in F508del patients.

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

“…Combinations of type I, II and III correctors restored 50%–100% of wild-type-level Phe508del CFTR biogenesis and stability in immortalized and primary human airway epithelia ( Veit et al, 2018 ). Concomitantly, the correctors decrease mucus concentration, relax mucus network ultrastructure, improve mucus transport and rheology of airway surface liquid, accelerate wound repair of the airway epithelium and change the plasma and cellular lipidome, in particular make the epithelial cells less susceptible to apoptosis by reducing the levels of ceramide ( Gardner et al, 2020 ; Liessi et al, 2020 ; Veit et al, 2021a ; Abu-Arish et al, 2022 ; Laselva and Conese, 2022 ; Ludovico et al, 2022 ; Morrison et al, 2022 ; Westhölter et al, 2022 ).…”