Cystic fibrosis (CF) is a genetic disease that affects the lungs, digestive system, reproductive system and sweat glands. Life expectancy has increased from only a few years in 1938, when the disease was first described, to approximately 37 years today. Identification of the mutated gene in 1989 initiated research into therapies targeted at the underlying defect. Dr. James L. Kreindler of Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, provided a review.
Damage to the pancreas was the first recognized manifestation of cystic fibrosis. Today, pancreatic enzyme replacement therapy enables patients to survive with adequate nutritional status. The healthy pancreas produces amylase, lipase, and protease that are necessary for digestion. Approximately 90 percent of CF patients are not able to produce sufficient amounts of these enzymes on their own.
“Survival of infancy and early childhood because of better nutrition resulted in lung disease rather than malnutrition being the most common cause of mortality in CF,” Kreindler reported. Patients face a vicious cycle of mucus retention, infection, inflammation, and tissue damage. Treatments in current use include physical methods for airway clearance, mucus-thinning agents, anti-inflammatory drugs, and antibiotics for pulmonary infections.
The source of CF symptoms has been identified as the cystic fibrosis transmembrane conductance regulator protein, CFTR. There are six classes of mutations to the gene that controls production of this protein. The CF genes are recessive, so an individual must inherit two copies to develop the disease. The protein controls the transport of ions, primarily chloride, in certain types of cells throughout the body. Research approaches include:
1. Viral-based gene therapy
2. Plasma DNA attached to lipids with positively charged ions
3. DNA nanoparticles
4. Drugs to alter the action of the CFTR gene
5. Drugs to alter the characteristics of the CFTR protein
Results from genetic studies have already made great progress in our understanding of CF, Kreindler concluded.