Effect of elexacaftor-tezacaftor-ivacaftor on nasal potential difference and lung function in Phe508del rats

is the most common cystic fibrosis transmembrane conductance regulator (CFTR) gene variant that results in the recessive genetic disorder cystic fibrosis (CF). The recent development of highly effective CFTR modulator therapies has led to significant health improvements in individuals with this muta...

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Bibliographic Details
Published in:Frontiers in pharmacology 2024-03, Vol.15, p.1362325
Main Authors: Reyne, Nicole, Cmielewski, Patricia, McCarron, Alexandra, Smith, Ronan, Schneider-Futschik, Elena, Eikelis, Nina, Pirakalathanan, Piraveen, Parsons, David, Donnelley, Martin
Format: Article
Language:English
Subjects:
CFTR modulator
cystic fibrosis
lung function
nasal potential difference
Pharmacology
rat model
X-ray velocimetry
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Summary:is the most common cystic fibrosis transmembrane conductance regulator (CFTR) gene variant that results in the recessive genetic disorder cystic fibrosis (CF). The recent development of highly effective CFTR modulator therapies has led to significant health improvements in individuals with this mutation. While numerous animal models of CF exist, few have a CFTR mutation that is amenable to the triple combination therapy elexacaftor-tezacaftor-ivacaftor (ETI). To determine the responsiveness of rats to ETI, a baseline nasal potential difference was measured. Subsequently, they received ETI daily for 14 days, after which post-treatment nasal potential difference, lung mechanics (via flexiVent) and lung ventilation (via X-ray Velocimetry) were assessed. Chloride ion transport in nasal airways was restored in rats treated with ETI, but neither lung mechanics nor ventilation were significantly altered. These findings validate the usefulness of this rat model for future investigations of modulator therapy in CF.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2024.1362325