title: Modifying disease in cystic fibrosis: current and future therapies on the horizon.
abstract: OBJECTIVE
  Recent 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.
  
  
  RESULTS
  Recent 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital and the University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Thida
authors.initials: T
authors.lastname: Ong
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D000627:Aminophenols / Q000627:therapeutic use*; D015415:Biomarkers; D002462:Cell Membrane / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D015316:Genetic Therapy / Q000639:trends*; D006801:Humans; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D009154:Mutation / Q000187:drug effects* / Q000235:genetics; D010641:Phenotype; D015363:Quinolones / Q000627:therapeutic use*; D019141:Respiratory System Agents / Q000627:therapeutic use*; D012462:Saline Solution, Hypertonic
chemical_list: D000627:Aminophenols; D015415:Biomarkers; C505032:CFTR protein, human; D005819:Genetic Markers; D015363:Quinolones; D019141:Respiratory System Agents; D012462:Saline Solution, Hypertonic; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D008353:Mannitol