Modifying disease in cystic fibrosis: current and future therapies on the horizon

Purpose of reviewRecent therapies directed at proximal targets within cystic fibrosis (CF) pathophysiology hold potential to modulate disease. This review highlights recent clinical trials and future therapies focused on these early steps of disease.Recent findingsRecent approval of a CF transmembrane conductance regulator (CFTR) protein modulator, ivacaftor (Kalydeco), has ignited a wave of investigations for other modulators directed at CFTR mutation classes. Gene replacement therapy continues to be pursued at a slower pace in early phase clinical trials. Airway surface liquid strategies such as dry-powder mannitol and alternate ion channel regulation are discussed as genotype-independent methods of early modulation.SummaryThe breadth of therapies for early targets of CF holds considerable hope to modify the natural history of this disease. Ongoing focus to develop novel markers of early disease state is paramount. The progress of drug development requires concurrent attention on a spectrum of targets to achieve maximal impact.