TY - JOUR
T1 - Correcting CFTR folding defects by small-molecule correctors to cure cystic fibrosis
AU - Mijnders, Marjolein
AU - Kleizen, Bertrand
AU - Braakman, Ineke
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Pharmacological intervention to treat the lethal genetic disease cystic fibrosis has become reality, even for the severe, most common folding mutant F508del CFTR. CFTR defects range from absence of the protein, misfolding that leads to degradation rather than cell-surface localization (such as F508del), to functional chloride-channel defects on the cell surface. Corrector and potentiator drugs improve cell-surface location and channel activity, respectively, and combination therapy of two correctors and a potentiator have shown synergy. Several combinations are in the drug-development pipeline and although the primary defect is not repaired, rescue levels are reaching those resembling a cure for CF. Combination therapy with correctors may also improve functional CFTR mutants and benefit patients on potentiator therapy.
AB - Pharmacological intervention to treat the lethal genetic disease cystic fibrosis has become reality, even for the severe, most common folding mutant F508del CFTR. CFTR defects range from absence of the protein, misfolding that leads to degradation rather than cell-surface localization (such as F508del), to functional chloride-channel defects on the cell surface. Corrector and potentiator drugs improve cell-surface location and channel activity, respectively, and combination therapy of two correctors and a potentiator have shown synergy. Several combinations are in the drug-development pipeline and although the primary defect is not repaired, rescue levels are reaching those resembling a cure for CF. Combination therapy with correctors may also improve functional CFTR mutants and benefit patients on potentiator therapy.
U2 - 10.1016/j.coph.2017.09.014
DO - 10.1016/j.coph.2017.09.014
M3 - Article
C2 - 29055231
SN - 1471-4892
VL - 34
SP - 83
EP - 90
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
ER -