Mucociliary transport in Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is the most common genetic life-threatening disease. It is defined as a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) membrane channel (1). Despite the monogenic cause of CF, there is a strikingly poor correlation between the CFTR genotype and clinical phenotype. Our incomplete understanding of the disease is linked to the very complex biology that underpins airway epithelial tissues, which are the main location of morbidity and mortality in the disease. CF is at heart a genetic disorder, but this is already not trivially a single gene problem: Previous studies have demonstrated major contributions to clinical outcomes of other genes although these remain poorly understood. As a consequence, therefore, we cannot currently predict from the genetics at an individual patient level any of i) the rate of decline of lung function, ii) response to a specific treatment, or iii) the risk of infection with particular pathogens. Of the nearly 2,000 CFTR mutations that have been identified so far (http://www.genet.sickkids.on.ca) (2), only the most common mutations expressed by large groups of subjects have been targeted for drug screening due to the high cost and time-consuming nature of clinical trials.