Novel Personalised Drugs for Cystic Fibrosis

摘要

Cystic fibrosis (CF) is a multiorgan genetic disease caused by defective function of CFTR, a plasma membrane chloride channel particularly expressed in epithelial cells. CF mutations have been grouped in six classes according to the mechanism through which they affect CFTR function: premature translation termination, impaired folding and stability, altered channel gating, reduced single channel conductance, aberrant RNA splicing, reduced persistence on cell surface. Each type of CFTR defect can be targeted by specific small molecules (correctors, potentiators, or readthrough agents) in order to restore CFTR function. Novel in vitro assays, based on intestinal organoids or nasal epithelial cells, can be used to identify the most appropriate treatment for each genotype. This approach paves the way for the development of personalized treatments for CF patients.