PT -期刊文章盟Becq Frederic AU - Mirval桑德拉盟——Carrez托马斯盟,桑德琳Manuella盟,钢坯Arnaud盟——Coraux Christelle AU - Sage,爱德华。非盟- Cantereau,安妮TI -拯救F508del-CFTR elexacaftor / tezacaftor / ivacaftor (Trikafta)在人类呼吸道上皮细胞被低估了由于存在ivacaftor援助- 10.1183/13993003.00671 -2021 DP - 2022年2月01 TA -欧洲呼吸杂志》第六PG - 2100671 - 59 IP - 2 4099 - //www.qdcxjkg.com/content/59/2/2100671.short 4100 - //www.qdcxjkg.com/content/59/2/2100671.full所以欧元和J2022 2月01;59 AB - Trikafta,目前主要治疗囊肿性纤维化(CF),展示了一个真正的临床益处。这两个折叠的三重联合治疗校正elexacaftor / tezacaftor (VX445 / VX661) +控制电位器ivacaftor (VX770)。在这项研究中,我们的目的是比较的属性F508del-CFTR在细胞治疗lumacaftor (VX809) tezacaftor, elexacaftor elexacaftor / tezacaftor有或没有ivacaftor。我们研究F508del-CFTR功能、成熟和膜本地化由美国商会和全细胞膜片箝记录、免疫印迹和immunolocalisation实验。与人类主要气道上皮细胞和细胞株CFBE博鸿泰表达F508del,我们发现,而组合elexacaftor / tezacaftor ivacaftor在拯救F508del-CFTR异常成熟,高效的顶端膜位置和功能,ivacaftor的存在限制了这些影响。基底F508del-CFTR短路电流明显增加了elexacaftor / tezacaftor ivacaftor和elexacaftor / tezacaftor与其他校正和参与细胞相比,效果依赖于ivacaftor和营地。这些结果表明,基底F508del-CFTR当前的水平可能会修正功效在CF细胞的标记。当细胞接受ivacaftor结合任何校正,随后F508del-CFTR电流是对急性ivacaftor,与雌性生殖道(囊性纤维化跨膜电导调节)电位器染料木黄酮和Cact-A1增加elexacaftor / tezacaftor ivacaftor和elexacaftor / tezacaftor-corrected F508del-CFTR电流。这些发现表明ivacaftor减少Trikafta的校正效果。 Thus, combining elexacaftor/tezacaftor with a different potentiator might improve the therapeutic efficacy for treating CF patients.Ivacaftor is not able to potentiate the function of Trikafta-rescued F508del-CFTR due to its destabilising effect. Ivacaftor does not preclude the use of different potentiators combined with Trikafta, so the beneficial effect of Trikafta is underestimated. https://bit.ly/3dxlsJb