Back to basics!

This unfortunate exhortation is usually the prelude to an outbreak of financial and sexual chicanery which would have caused comment even in the declining years of Imperial Rome (although not perhaps today in the same city). But this is the current exciting cystic fibrosis (CF) rallying cry. The treatment of CF has traditionally been fire fighting—treat the downstream consequences of cystic fibrosis transmembrane regulator (CFTR) dysfunction, like infection, inflammation and mucus hypersecretion. In the more than 20 years since the discovery of the CF gene, a series of focused studies have led to profound discoveries of the basic biology of CFTR and therefore to specific designer therapies to correct the basic defect, discovered by high-throughput screening of thousands of compounds. G551D CFTR reaches the apical cell membrane but functions abnormally. The ‘potentiator’ VX-770 has been shown to have dramatic effects in CF patients with this rare mutation (about 5% of the population), for example, halving sweat chloride (see NEJM 2011;365:1663-72). The most common mutation, ΔF₅₀₈, results in a protein which …