AUTHOR=Reyne Nicole , Cmielewski Patricia , McCarron Alexandra , Smith Ronan , Eikelis Nina , Pirakalathanan Piraveen , Parsons David , Donnelley Martin 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1362325

DOI=10.3389/fphar.2024.1362325

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold><italic>Phe508del</italic> 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).</p><p><bold>Methods:</bold> To determine the responsiveness of <italic>Phe508del</italic> 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.</p><p><bold>Results:</bold> Chloride ion transport in nasal airways was restored in <italic>Phe508del</italic> rats treated with ETI, but neither lung mechanics nor ventilation were significantly altered.</p><p><bold>Discussion:</bold> These findings validate the usefulness of this rat model for future investigations of modulator therapy in CF.</p>