Fajac I, Girodon E
AP-HP, Hôpital Cochin, Service de Physiologie et Explorations Fonctionnelles, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
APHP, Centre-Université de Paris, Hôpital Cochin, Laboratoire de Génétique et Biologie Moléculaires, Paris, France.
Arch Pediatr. 2020 Feb;27 Suppl 1:eS41-eS44. doi: 10.1016/S0929-693X(20)30050-6.
Since the cloning of the CFTR gene 30 years ago, research aiming at understanding how CFTR mutations translate to abnormal synthesis or function of the CFTR protein has opened the way to genomically-guided therapy to improve CFTR function. A CFTR potentiator to enhance CFTR channel function has been approved in 2012 for specific and quite rare mutations. Subsequently, combinations of a corrector to increase CFTR expression at the cell membrane, plus a potentiator, have been approved for patients homozygous for the p.Phe508del mutation. To obtain robust correction of CFTR, new combinations of drugs are being studied. A triple combination associating two correctors and one potentiator is very promising and if data of clinical trials are confirmed, it could be a robust and well tolerated CFTR modulator for patients bearing at least one p.Phe508del mutation. Many other strategies are also in development to make these genomically-guided treatments available to all patients with CF. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
自30年前克隆CFTR基因以来，旨在了解CFTR突变如何转化为CFTR蛋白异常合成或功能的研究，为基因组指导治疗以改善CFTR功能开辟了道路。一种增强CFTR通道功能的CFTR增强剂于2012年获批用于特定且相当罕见的突变。随后，一种增加CFTR在细胞膜上表达的校正剂与一种增强剂的联合用药已获批用于携带p.Phe508del突变纯合子的患者。为了实现对CFTR的有效校正，正在研究新的药物组合。一种将两种校正剂和一种增强剂联合使用的三联组合非常有前景，如果临床试验数据得到证实，它可能成为一种对至少携带一个p.Phe508del突变的患者有效且耐受性良好的CFTR调节剂。许多其他策略也在开发中，以使所有囊性纤维化患者都能接受这些基因组指导的治疗。© 2020法国儿科学会。由爱思唯尔马松出版社出版。保留所有权利。
