What Do We Know About Gene Therapy and Cystic Fibrosis?

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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—cause 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 Research Offers Promise of a Cure for Cystic Fibrosis

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 the 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, and find out how long treatment should last and how often it needs to be repeated.

The first cystic fibrosis gene therapy experiments 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.

Genetic Research May Lead to New Drugs to Treat Cystic Fibrosis

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.

Gene Database Speeds Research

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.

“What Do We Know About Gene Therapy and Cystic Fibrosis? was originally published by the National Institutes of Health.”