From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations

More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or…

• TD
  Tobacco-Related Disease Research Program
• CF
  Cystic Fibrosis Foundation Therapeutics

  Award: SHEPPA14XX0
• CF
  Cystic Fibrosis Trust
• NI
  National Institutes of Health

  Awards: HL095524, R01-DK068196, DK072506, P30-DK072506, NIH R01