Cystic fibrosis (CF) is the most common, fatal genetic disease in the United States. About 30,000 people in the United States have the disease. CF causes the body to produce thick, sticky mucus that clogs the lungs, leads to infection, and blocks the pancreas, which stops digestive enzymes from reaching the intestine where they are required in order to digest food.
Mutations in a single gene - the Cystic Fibrosis Transmembrane Regulator (CFTR) gene - causes CF. The gene was discovered in 1989. Since then, more than 900 mutations of this single gene have been identified.
In normal cells, the CFTR protein acts as a channel that allows cells to release chloride and other ions. But in people with CF, this protein is defective and the cells do not release the chloride. The result is an improper salt balance in the cells and thick, sticky mucus. Researchers are focusing on ways to cure CF by correcting the defective gene, or correcting the defective protein.
Gene therapy offers great promise for life-saving treatment for CF patients since it targets the cause of CF rather than just treating symptoms. Gene therapy for CF had its start in 1990, when scientists successfully corrected faulty CFTR genes by adding normal copies of the gene to laboratory cell cultures.
In 1993, the first experimental gene therapy treatment was given to a patient with CF. Researchers modified a common cold virus to act as a delivery vehicle - or "vector"- carrying the normal genes to the CFTR cells in the airways of the lung.
Subsequent studies have tested other methods of gene delivery, such as fat capsules, synthetic vectors, nose drops or drizzling cells down a flexible tube to CFTR cells lining the airways of lungs. Researchers are now testing aerosol delivery using nebulizers.
But finding the best delivery system for transporting normal CFTR genes is only one problem that scientists must solve to develop an effective treatment for CF. Scientists must also determine the life span of affected lung cells, identify the "parent cells" that produce CFTR cells, find out how long treatment should last and how often it needs to be repeated.
The first cystic fibrosis gene therapy experiments have involved lung cells because these cells are readily accessible and because lung damage is the most common, life-threatening problem in CF patients. But scientists hope that the technologies being developed for lung cells will be adapted to treat other organs affected by CF.
Another research breakthrough offers a promising approach to treating cystic fibrosis. Researchers at the University of Washington's Genome Center and at PathoGenesis Corporation have completed a genetic map for the Pseudomonas aeruginosa bacterium. This bacterium is the most common cause of chronic and fatal lung infections for people with CF. Scientists hope to use their knowledge of this bacterium's genetic sequence to develop innovative drugs for treating infections caused by P. aeruginosa.
As the amount of information about CF grows, scientists have recognized the need to share their research findings. To facilitate this sharing of information, the Cystic Fibrosis Foundation funds Cystic Fibrosis Foundation Therapeutics (CFFT) located at The University of North Carolina Chapel Hill. The center is becoming a repository for data derived from gene expression studies. By pooling information, researchers hope to accelerate the process of finding a cure for CF.
CF has a variety of symptoms, including very salty-tasting skin, a persistent cough and excessive appetite but poor weight gain. The "sweat test" - which measures the amount of salt in sweat - is the standard diagnostic test for those with symptoms. A high salt level indicates CF.
But one in 31 Americans - more than 10 million people - are symptom-less carriers of the defective CF gene and can pass on the defective gene to their children. To develop CF, a child must inherit a defective gene from both parents. If both parents are carriers, there is a 25 percent chance that each child they conceive will have CF, and a 50 percent chance that the child will be a carrier.
The purpose of carrier testing - a laboratory test done on a sample of blood or saliva - is to see if a couple is at risk for giving birth to a child with CF. Carrier testing is not infallible. It cannot detect all of the CF gene mutations. In rare cases, a person can have a normal test result and still be a CF carrier.
If both parents are carriers, they may want to consult with a genetic counselor for help in deciding whether to conceive or whether to have a fetus tested for CF.
Prenatal testing for CF can be done around the 11th week of pregnancy using chorionic villi sampling (CVS). This involves removing a tiny piece of the placenta. Or, the fetus can be tested with amniocentesis, around the 16th week of pregnancy. In this procedure, a needle is used to take amniotic fluid surrounding the baby for testing. Since CF cannot be treated before birth, the purpose of prenatal testing is to prepare parents to care for a baby with special health needs, or to make a decision about terminating the pregnancy.
Research on Cystic Fibrosis is currently being conducted at the Medical Genetics Branch of the National Human Genome Research Institute.
Current NHGRI Clinical Trials Include:
Last Updated: December 27, 2013