REVIEW   

Minerva Pediatrica 2019 June;71(3):287-96

DOI: 10.23736/S0026-4946.19.05506-3

Copyright © 2019 EDIZIONI MINERVA MEDICA

lingua: Inglese

Mutation-specific therapies and drug repositioning in cystic fibrosis

Valeria R. VILLELLA ¹, Antonella TOSCO ², Speranza ESPOSITO ¹, Gianni BONA ³, Valeria RAIA ², Luigi MAIURI ^{1, 3} ✉

¹ European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy; ² Unit of Pediatrics, Regional Cystic Fibrosis Center, Department of Translational Medical Sciences, Federico II University, Naples, Italy; ³ Department of Health Sciences, University of Eastern Piedmont, Novara, Italy

Cystic fibrosis (CF) is an inherited, prematurely lethal rare disease affecting more than 85,000 people worldwide. CF is caused by more than 2000 loss-of-function mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). This review summarizes recent advances in the etiological therapies of CF that aim at repairing the functional defect of CFTR by means of CFTR modulators. We will discuss the state of art of the mutation-specific treatments that are designed to target different steps of the CFTR biogenesis perturbed by mutations in CFTR gene. Moreover, we will discuss how drug repositioning, namely the use of drugs already approved for the treatment of other human diseases, may be repurposed in CF patients to circumvent CFTR dysfunction. Finally, we highlight how the combined use of two or more compounds acting on different disease mechanisms is required to achieve clinical benefit in CF population.

KEY WORDS: Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; Drug repositioning