The cloning and availability of the cDNA provided a key tool that has greatly increased our knowledge of the genetics and pathophysiology of CF and the normal functions of the cystic fibrosis transmembrane regulator, CFTR. We now know that CFTR functions both as a channel and a regulator of other channels These functions act to maintain lung fluid balance, properly hydrate mucous, and provide a proper environment for the functioning of natural antibacterial defense molecules. We also know that the most common mutation results in a missing phenylalanine at position 508 (AF508), causing most of the mutant protein to be degraded before reaching its proper location in the cell The portion that is processed to the plasma membrane is not fully functional. Recently, our new knowledge is being applied to generate novel therapies that directly attack the dysfunction of mutant CFTR. The challenge is two fold, to overcome the biosynthetic defect in the AF508 mutant and/or to stimulate that portion which does traffic to the plasma membrane. Drugs are being developed to act as chemical chaperones that overcome the trafficking defect of CFTR. Likewise, drugs such as phosphodiesterase inhibitors are being explored to stimulate mutant forms of CFTR that escape degradation. Finally, with the cloning of the CF gene, it became feasible to introduce a new copy of the gene into defective cells by gene therapy.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology