The researchers studied the interaction between CFTR proteins (mutated and wild type) and some correctors by the use of in-vitro experimental system based on mammalian cells. The project results report that lumacaftor (VX809), tezacaftor (VX661) and VX325 specifically improve the expression and maturation of the first half of CFTR. The corr4a corrector seems to affect the expression of the second half of the CFTR. The interaction of the derivative 2a (a molecule derived from Lumacaftor) and of the correctors elexacaftor (VX445) and FCG seems to be with the NBD1 and NBD2 of CFTR respectively. The researchers with this project have gained knowledge about the mechanisms of action of the available and new correctors. In addition, the researchers have obtained useful information to design more specific correctors or create more effective correctors combinations.

Pubblications

• Amico G, Brandas C, Moran O, Baroni D. Unravelling the Regions of Mutant F508del-CFTR More Susceptible to the Action of Four Cystic Fibrosis Correctors. Int J Mol Sci. 2019 Nov 1;20(21):5463. doi: 10.3390/ijms20215463. PMID: 31683989; PMCID: PMC6862496.