Novel, mechanism-based therapies for cystic fibrosis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Rubenstein
Ronald C
RC
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Pennsylvania 19104, USA. rrubenst@mail.med.upenn.edu
D000818:Animals; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects; D053503:Epithelial Sodium Channels; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D009154:Mutation; D015222:Sodium Channels / Q000187:drug effects
C505032:CFTR protein, human; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator