The prospects of pharmacotherapy for cystic fibrosis

To summarize, no effective treatment by drugs is available for CF at the present time. Nevertheless, until a decade ago there were virtually no compounds known that could activate CFTR, whereas today there are many different chemical structures having this property. Much has been learned about molecular pharmacology of CFTR and its most common mutant, deltaF508 CFTR, that will provide new insights for drug design. Clearly a compound that could activate both trafficking and opening of deltaF508 CFTR could have a major impact, provided toxicity and tolerance were acceptable. Even so only the effects on chloride transport would be alleviated, while appreciating that other functions of CFTR may remain uncorrected. There is also a concern that bypassing the quality control mechanisms of the cell to allow deltaF508 CFTR to be trafficked may have wider implications for other improperly formed proteins. Rather than direct drug treatment strategies towards CFTR an alternative approach is to involve other cellular mechanisms to achieve the desired result. Here activation of calcium activated chloride channels plus blockade of epithelial sodium channels could restore the electrolyte balance necessary for efficient mucociliary clearance. Again this approach aims only to regularize the effects of CF on chloride transport and would have no effect on fluid production by the serous cells of submucosal glands.