Pharmacological treatment of the biochemical defect in cystic fibrosis airways

The understanding of the biochemical defect in cystic fibrosis (CF) has adv anced considerably since discovery of the CF gene in 1989 and characterizat ion of its product. Studies showing that the abnormality in chloride flux c ould be corrected by transfection of wild-type cystic fibrosis transmembran e conductance regulator (CFTR) complimentary deoxyribonucleic acid (cDNA) h ave led to gene therapy trials on both sides of the Atlantic, However, gene therapy as a treatment for CF has) et to be realized. Pharmacological manipulation of the biochemical defect may provide an alter native or complementary approach to treatment. This review will discuss pha rmacological agents in development which could correct the abnormal ion mov ement, The mechanisms of action of these pharmacological agents can be divided bro adly into drugs which affect the most common CF mutation, Delta F508, which increase trafficking of the mutant CF protein to the apical membrane; drug s which increase chloride secretion; and drugs which reduce sodium reabsorp tion across the apical membrane, Treatment options for cystic fibrosis have developed rapidly since discover y of the cystic fibrosis gene over a decade ago. The targeting of specific therapies for particular cystic fibrosis genotypes and the use of combinati on treatments of chloride channel openers with sodium channel blockers are likely to be key advances in the nest decade.