Genomically-guided therapies: A new era for cystic fibrosis

Abstract

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.