Cystic fibrosis as a paradigmatic disease in bringing science to the bedside.

Abstract

Cystic fibrosis (CF) is a recessive disorder caused by mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR), a chloride/bicarbonate channel that balances fluid homeostasis in epithelia. CFTR dysfunction results in chronic lung infections, pancreatic insufficiency, and salty sweat. Since the discovery of the CFTR gene in 1989, a unique scientific community in both academia and industry has significantly increased our understanding of CF mechanisms. Such knowledge led to spectacular advancements in treatment, from symptom management to CFTR modulators (CFTRm) that alter the mutant protein properties in a mutation-specific way, significantly improving life quality and expectancy of people with CF (pwCF). Emerging genotype-agnostic approaches, such as gene/mRNA therapy, hold promise for future curative treatments for all pwCF. In parallel, precision medicine is revolutionizing CF care through patient-specific therapies, namely for pwCF with genotypes not eligible for CFTRm. However, challenges remain, including high treatment costs, accessibility issues, variable patient responses, and, importantly, the high cancer propensity in pwCF. CF is a model for translational medicine, highlighting the relevance of fundamental research. Insights gained from CF research may also inform therapeutic advancements for other (genetic) diseases.