Molecular Diagnosis & Therapy

, Volume 10, Issue 5, pp 293–301 | Cite as

Targeted Therapy for Cystic Fibrosis

Cystic Fibrosis Transmembrane Conductance Regulator Mutation-Specific Pharmacologic Strategies
  • Ronald C. Rubenstein
Genetic Disorders


Cystic fibrosis (CF) results from the absence or dysfunction of a single protein, the CF transmembrane conductance regulator (CFTR). CFTR plays a critical role in the regulation of ion transport in a number of exocrine epithelia. Improvement or restoration of CFTR function, where it is deficient, should improve the CF phenotype. There are >1000 reported disease-causing mutations of the CFTR gene. Recent investigations have afforded a better understanding of the mechanism of dysfunction of many of these mutant CFTRs, and have allowed them to be classified according to their mechanism of dysfunction. These data, as well as an enhanced understanding of the role of CFTR in regulating epithelial ion transport, have led to the development of therapeutic strategies based on pharmacologic enhancement or repair of mutant CFTR dysfunction. The strategy, termed ‘protein repair therapy’, is aimed at improving the regulation of epithelial ion transport by mutant CFTRs in a mutation-specific fashion. The grouping of CFTR gene mutations, according to mechanism of dysfunction, yields some guidance as to which pharmacologic repair agents may be useful for specific CFTR mutations. Recent data has suggested that combinations of pharmacologic repair agents may be necessary to obtain clinically meaningful CFTR repair. Nevertheless, such strategies to improve mutant CFTR function hold great promise for the development of novel therapies aimed at correcting the underlying pathophysiology of CF.


Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Chloride Transport Cystic Fibrosis Transmembrane Conductance Regulator Mutation Cystic Fibrosis Transmembrane Conductance Regulator Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author’s research is supported by grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (grant numbers R01–DK58046 and R01–DK54354), the Cystic Fibrosis Foundation, and an Established Investigator Award from the American Heart Association.

The author has no conflict of interest that is directly relevant to the content of this review.


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© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Division of Pulmonary Medicine and Cystic Fibrosis CenterChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Department of PediatricsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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