Therapeutic approaches to CFTR dysfunction: from discovery to drug development

Hongyu Li, Emanuela Pesce, David N. Sheppard, Ashvani K. Singh, Nicoletta Pedemonte*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

33 Citations (Scopus)
366 Downloads (Pure)


Cystic fibrosis (CF) mutations have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. They disrupt its processing to and stability at the plasma membrane and function as an ATP-gated Cl channel. Here, we review therapeutic strategies to overcome defective CFTR processing and stability. Because CF mutations have multiple impacts on the assembly of CFTR protein, combination therapy with several pharmacological chaperones is likely to be required to rescue mutant CFTR expression at the plasma membrane. Alternatively, proteostasis regulators, proteins which regulate the synthesis, intracellular transport and membrane stability of CFTR might be targeted to enhance the plasma membrane expression of mutant CFTR. Finally, we consider an innovative approach to bypass CFTR dysfunction in CF, the delivery of artificial anion transporters to CF epithelia to shuttle Cl across the apical membrane. The identification of therapies or combinations of therapies, which rescue all CF mutations, is now a priority.

Original languageEnglish
Pages (from-to)S14-S21
Number of pages8
JournalJournal of Cystic Fibrosis
Issue number2
Early online date12 Sept 2017
Publication statusPublished - 1 Mar 2018


  • CFTR CI-channel
  • F508del-CFTR
  • CFTR correctors
  • Pharmacological chaperones
  • Proteostasis regulators
  • Artificial anion transporters (anionophores)


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