Abstract
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 Ca2+-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.
| Original language | English |
|---|---|
| Journal | Journal of Cystic Fibrosis |
| Volume | 10 |
| Issue number | SUPPL. 2 |
| DOIs | |
| Publication status | Published - Jul 2011 |
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Keywords
- Airway surface fluid
- CFTR
- CFTR correctors
- CFTR potentiators
- ENaC
- F508del
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Pediatrics, Perinatology, and Child Health
Cite this
Pharmacological therapy for cystic fibrosis : From bench to bedside. / Becq, Frédéric; Mall, Marcus A.; Sheppard, David N.; Conese, Massimo; Zegarra-Moran, Olga.
In: Journal of Cystic Fibrosis, Vol. 10, No. SUPPL. 2, 07.2011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacological therapy for cystic fibrosis
T2 - From bench to bedside
AU - Becq, Frédéric
AU - Mall, Marcus A.
AU - Sheppard, David N.
AU - Conese, Massimo
AU - Zegarra-Moran, Olga
PY - 2011/7
Y1 - 2011/7
N2 - 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 Ca2+-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.
AB - 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 Ca2+-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.
KW - Airway surface fluid
KW - CFTR
KW - CFTR correctors
KW - CFTR potentiators
KW - ENaC
KW - F508del
UR - http://www.scopus.com/inward/record.url?scp=79958104493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958104493&partnerID=8YFLogxK
U2 - 10.1016/S1569-1993(11)60018-0
DO - 10.1016/S1569-1993(11)60018-0
M3 - Article
C2 - 21658632
AN - SCOPUS:79958104493
VL - 10
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
SN - 1569-1993
IS - SUPPL. 2
ER -