CFTR potentiators partially restore channel function to A561E-CFTR a cystic fibrosismutant with a similar mechanism of dysfunction as F508del-CFTR

摘要

Background and PurposeDysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel causes the genetic disease cystic fibrosis (CF). Towards the development of transformational drug therapies for CF, we investigated the channel function and action of CFTR potentiators on A561E, a CF mutation found frequently in Portugal. Like the most common CF mutation F508del, A561E causes a temperature-sensitive folding defect that prevents CFTR delivery to the cell membrane and is associated with severe disease.