title: New pulmonary therapies directed at targets other than CFTR.
abstract: Our current understanding of the pathogenesis of cystic fibrosis (CF) lung disease stresses the importance of the physical and chemical properties of the airway surface liquid (ASL). In particular, the loss of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel function in CF reduces the volume and fluidity of the ASL, thus impairing mucociliary clearance and innate antimicrobial mechanisms. Besides direct approaches to restoring mutant CFTR function, alternative therapeutic strategies may also be considered to correct the basic defect of impaired salt and water transport. Such alternative strategies are focused on the restoration of mucociliary transport by (1) reducing sodium and fluid absorption by inhibiting the ENaC channel; (2) activating alternative chloride channels; and (3) increasing airway surface hydration with osmotic agents. Therapeutic approaches directed at targets other than CFTR are attractive because they are potentially useful to all patients irrespective of their genotype. Clinical trials are underway to test the efficacy of these approaches.
authors.affiliation: Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. scott_donaldson@med.unc.edu
authors.forename: Scott H
authors.initials: SH
authors.lastname: Donaldson
authors.forename: Luis
authors.initials: L
authors.lastname: Galietta
mesh_terms: D000075369:Anoctamin-1; D001430:Bacteriocins / Q000627:therapeutic use; D018118:Chloride Channels / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000627:therapeutic use; D004234:Diuretics, Osmotic / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers / Q000627:therapeutic use; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D008353:Mannitol / Q000627:therapeutic use; D009079:Mucociliary Clearance / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use; D012964:Sodium / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D001430:Bacteriocins; C505032:CFTR protein, human; D018118:Chloride Channels; D003845:Deoxycytosine Nucleotides; D004234:Diuretics, Osmotic; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D009363:Neoplasm Proteins; D010455:Peptides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C040522:duramycin; D008353:Mannitol; C465279:denufosol tetrasodium; D012964:Sodium; D014529:Uridine