Fig. 1. From Structure and Function of the CFTR Chloride Channel, Physiol. Rev. 79:23-45 (1999)
Fig. 2. Schematic representation of proposed CFTR structure. CFTR is made up of five domains: two membrane-spanning domains that form the chloride ion channel, two nucleotide-binding domains that bind and hydrolyze ATP and a regulatory domain.
Cystic Fibrosis
Cystic fibrosis (CF) is the most common fatal, inherited disease in the United States. It is a genetic disorder resulting from the inheritance of a defective autosomal recessive gene. The average life expectancy of the 30,000 CF patients currently alive in the U.S. is under 30 years.
The gene responsible for CF codes for the cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP regulated Cl-ion channel found in the apical membranes of secretory epithelial cells. Mutations in CTFR disrupt epithelial ion transport and can lead to respiratory failure, pancreatic insufficiency, infertility, as well as a range of other defects. There is, at present, no cure for the disease.
Although there has been extraordinary progress, complexities in the biology of the diseased lung pose several inherent difficulties for gene therapy; since CTFR is expressed in cells throughout the superficial epithelial as well as cells in the submucosal glands, it will be difficult to reconstitute precisely the normal expression of the CF gene using current techniques. There is a substantial need for parallel therapeutic strategies. The long range goal of our research is the design of therapeutic technologies based on a fundamental biophysical understanding of the cascade of events that contribute to respiratory failure in cystic fibrosis.