David Noel Sheppard, PhDProfessor of Physiology,
University of Bristol,
The genetic disease cystic fibrosis (CF) is caused by dysfunction of the epithelial anion channel, cystic fibrosis transmembrane conductance regulator (CFTR). Orally-bioavailable CFTR modulators termed CFTR correctors and potentiators that directly target defective CFTR anion channels have transformed the treatment of CF. This presentation will first review how the predominant CF-causing CFTR variant, F508del, disrupts the plasma membrane expression, stability and function of CFTR. Then, single-channel studies to elucidate how the triple combination therapy elexacaftor-tezacaftor-ivacaftor rescue the F508del-CFTR chloride channel will be discussed.