Novel, mechanism-based therapies for cystic fibrosis

Cystic fibrosis results from disruption of the biosynthesis or function of the cystic fibrosis transmembrane conductance regulator. Cystic fibrosis transmembrane conductance regulator plays a critical role in the regulation of epithelial ion transport. Restoration of cystic fibrosis transmembrane conductance regulator function should improve the cystic fibrosis phenotype.

Recent investigations affording a better understanding of the mechanism of dysfunction of mutant cystic fibrosis transmembrane conductance regulators, as well as the roles of cystic fibrosis transmembrane conductance regulator in regulating epithelial ion transport, have led to development of therapeutic strategies based on repair or bypass of mutant cystic fibrosis transmembrane conductance regulator dysfunction. The former strategy, coined 'protein repair therapy,' is aimed at improving or restoring the function of mutant cystic fibrosis transmembrane conductance regulators, whereas the latter approach aims to augment epithelial ion transport to compensate for the absent function mutant cystic fibrosis transmembrane conductance regulator.

Strategies to improve mutant cystic fibrosis transmembrane conductance regulator function or to bypass mutant cystic fibrosis transmembrane conductance regulator function hold great promise for development of novel therapies aimed at correcting the underlying pathophysiology of cystic fibrosis.