Huang Yunjie, Gonzales Cordova Jorge Moises, Penrod Sarah, Bendy Lisa Lynn, Cheng Pi Chun, Sanders Don B, Davis Michael Denning, Gaston Benjamin, Chmiel James Francis
Division of Pediatric Pulmonology, Allergy, and Sleep Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Int J Mol Sci. 2025 May 31;26(11):5306. doi: 10.3390/ijms26115306.
Cystic Fibrosis (CF) is a common genetic disease in the United States, resulting from mutations in the gene. CFTR modulators, particularly Elexacaftor/Tezacaftor/Ivacaftor (ETI), have significantly improved clinical outcomes for patients with CF. However, many CFTR mutations are not eligible for CFTR modulator therapy due to their rarity. In this study, we report that a patient carrying rare complex CFTR mutations, c.1680-877G>T and c.3067_3072delATAGTG, showed positive clinical outcomes after ETI treatment. We demonstrate that ETI was able to increase the expression of CFTR harboring c.3067_3072delATAGTG in a heterologous system. Importantly, patient-derived nasal epithelial cells in an air-liquid interface (ALI) culture showed improved CFTR function following ETI treatment. These findings supported the initiation of ETI with the patient. Retrospective studies have suggested that the patient has shown small but steady improvement over the past two years in several clinical metrics, including lung function, body mass index (BMI), and sweat chloride levels. Our studies suggest that ETI could be beneficial for patients carrying c.3067_3072delATAGTG.
囊性纤维化（CF）是美国一种常见的遗传疾病，由该基因的突变引起。CFTR调节剂，特别是依列卡托/替扎卡托/依伐卡托（ETI），显著改善了CF患者的临床结局。然而，许多CFTR突变由于其罕见性而不符合CFTR调节剂治疗的条件。在本研究中，我们报告了一名携带罕见复杂CFTR突变c.1680-877G>T和c.3067_3072delATAGTG的患者在接受ETI治疗后显示出阳性临床结局。我们证明ETI能够在异源系统中增加携带c.3067_3072delATAGTG的CFTR的表达。重要的是，在气液界面（ALI）培养中患者来源的鼻上皮细胞在ETI治疗后显示出改善的CFTR功能。这些发现支持了对该患者使用ETI治疗。回顾性研究表明，在过去两年中，该患者在包括肺功能、体重指数（BMI）和汗液氯化物水平在内的几个临床指标上有虽小但稳定的改善。我们的研究表明，ETI可能对携带c.3067_3072delATAGTG的患者有益。
