Pharmacological therapy for cystic fibrosis: from bench to bedside

J Cyst Fibros. 2011 Jun;10 Suppl 2:S129-45. doi: 10.1016/S1569-1993(11)60018-0.


With knowledge of the molecular behaviour of the cystic fibrosis transmembrane conductance regulator (CFTR), its physiological role and dysfunction in cystic fibrosis (CF), therapeutic strategies are now being developed that target the root cause of CF rather than disease symptoms. Here, we review progress towards the development of rational new therapies for CF. We highlight the discovery of small molecules that rescue the cell surface expression and defective channel gating of CF mutants, termed CFTR correctors and CFTR potentiators, respectively. We draw attention to alternative approaches to restore epithelial ion transport to CF epithelia, including inhibitors of the epithelial Na(+) channel (ENaC) and activators of the Ca(2+)-activated Cl(-) channel TMEM16A. The expertise required to translate small molecules identified in the laboratory to drugs for CF patients depends on our ability to coordinate drug development at an international level and our ability to provide pertinent biological information using suitable disease models.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anoctamin-1
  • Chloride Channels
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / agonists*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Drug Design*
  • Drug Industry / organization & administration
  • Drug Industry / trends
  • Epithelial Sodium Channel Blockers*
  • Humans
  • Membrane Proteins / agonists*
  • Neoplasm Proteins / agonists*


  • ANO1 protein, human
  • Anoctamin-1
  • CFTR protein, human
  • Chloride Channels
  • Epithelial Sodium Channel Blockers
  • Membrane Proteins
  • Neoplasm Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator