Cystic Fibrosis: An Update
The most common fatal genetic (inborn) disease in North American among Caucasians is cystic fibrosis (CF). Approximately 30,000 American suffer from CF and another 10 million persons are silent carriers of the defective gene. The gene that should produce a normal protein called CFTR is defective in patients with CF; the CFTR normally channels chloride ions (Cl-) out of cells, especially those in the lungs and pancreas. When the channel is blocked due to improper folding of the CFTR, Cl- cannot be properly moved. A number of disturbances occur – in the lung, for example, the mucus becomes as thick as cooked oatmeal, providing an ideal environment for bacteria such as Pneumococcus to grow.
The defective gene that results in CF was first identified in 1989. Gene therapy approaches, which attempt to introduce normal CFTR genes (using viruses to carry them) to CF patients, emerged in the 1990s as a promising avenue for development. Work is still being done to try to solve the problem of getting these viruses through the epithelial lining in the airways of CF patients.
As the studies of gene therapy continue, a number of drugs are being tested to find ways to treat CF. One interesting approach that may be of value to some patients is the small molecule PTC124. This orally available molecule was designed to read through premature stop codes in RNA translation causing CFTR to be improperly synthesized.
Another approach is to find drugs that can wedge open the gate allowing the chloride ions to pass. However, there are 1,600 known mutations to the CF gene, making the search difficult. There has been progress in opening the gate with at least two new drugs; at present these are being tested with some success in humans. A significant adjunct to this work is that some of the drugs that affect the nonsense codes is that this approach will find application in other genetic diseases such as Duchene Muscular dystrophy.