Cystic fibrosis

Abstract

Cystic fibrosis is a rare genetic disease caused by mutations in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). The discovery of CFTR in 1989 has enabled the unravelling of disease mechanisms and, more recently, the development of CFTR-directed therapeutics that target the underlying molecular defect. The CFTR protein functions as an ion channel that is crucial for correct ion and fluid transport across epithelial cells lining the airways and other organs. Consequently, CFTR dysfunction causes a complex multi-organ disease but, to date, most of the morbidity and mortality in people with cystic fibrosis is due to muco-obstructive lung disease. Cystic fibrosis care has long been limited to treating symptoms using nutritional support, airway clearance techniques and antibiotics to suppress airway infection. The widespread implementation of newborn screening for cystic fibrosis and the introduction of a highly effective triple combination CFTR modulator therapy that has unprecedented clinical benefits in up to 90% of genetically eligible people with cystic fibrosis has fundamentally changed the therapeutic landscape and improved prognosis. However, people with cystic fibrosis who are not eligible based on their CFTR genotype or who live in countries where they do not have access to this breakthrough therapy remain with a high unmet medical need.