Reyne Nicole, Cmielewski Patricia, McCarron Alexandra, Smith Ronan, Schneider-Futschik Elena, Eikelis Nina, Pirakalathanan Piraveen, Parsons David, Donnelley Martin
Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Front Pharmacol. 2024 Mar 13;15:1362325. doi: 10.3389/fphar.2024.1362325. eCollection 2024.
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.
是导致隐性遗传病囊性纤维化（CF）的最常见囊性纤维化跨膜传导调节因子（CFTR）基因突变。高效CFTR调节剂疗法的最新进展已使携带这种突变的个体的健康状况得到显著改善。虽然存在多种CF动物模型，但很少有CFTR突变适合三联组合疗法依列卡托-替扎卡托-依伐卡托（ETI）。为了确定大鼠对ETI的反应性，测量了基线鼻电位差。随后，它们连续14天每天接受ETI治疗，之后评估治疗后的鼻电位差、肺力学（通过flexiVent）和肺通气（通过X射线测速法）。接受ETI治疗的大鼠鼻气道中的氯离子转运得以恢复，但肺力学和通气均未发生显著改变。这些发现证实了该大鼠模型对于未来CF调节剂疗法研究的有用性。
