The basic defect in cystic fibrosis (CF) is the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated ion channel permeable to chloride and bicarbonate. Correction of the basic defect may be obtained by rescuing the mutant CFTR proteins with drugs that specifically target the alterations caused by CF mutations. For example, small molecules known as "potentiators" are able to improve the activity of CFTR proteins with channel gating mutations. Instead, "correctors" may contrast the destabilising effects that the Phe508del mutation, the most frequent among CF patients, causes to CFTR protein. Recent studies suggest the possibility that a high extent of Phe508delCFTR rescue may only be obtained by a combination of correctors having different mechanisms of action. Alternative strategies to correct the CF ion-transport defect are based on the stimulation of alternative chloride channels, such as TMEM16A or SLC26A9, or the improvement of airway surface hydration using osmotically active agents.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine