Cystic fibrosis is a nasty inherited chronic illness. It affects the lungs and digestive system of about 30,000 children and adults in the United States and an estimated 70,000 people worldwide.
CF is the most common lethal genetic disease in the Caucasian population, affecting one in 3300 births. Other ethnic populations are affected less frequently, ranging from one in 10,000 – 15,000 births in Hispanic and African-American populations, to one in 30,000 Asian births.
The underlying cause is a mutation in the ion channel gene CFTR (cystic fibrosis transmembrane conductance regulator). This gene is responsible for controlling salt and water transport across the cells lining the lung, pancreas, and other organs.
When this gene is abnormal, secretions in these organs become dehydrated and sticky, and eventually clog airways and may block other organs (pancreas, intestines, male reproductive tract, bile ducts) as well.
Not too many decades ago, few children lived to attend elementary school. Today, with advances in research and treatment, the median age of survival for children diagnosed with CF is more than 37 years. Many with the disease can now expect to live beyond their 30s and 40s.
Scientists have worked for 20 years to perfect gene therapy for the treatment of cystic fibrosis. In recent research, UNC scientists have found what may be the most efficient way to deliver a corrected gene to lung cells collected from cystic fibrosis patients. They also showed that it may take this high level of efficiency for cystic fibrosis (CF) patients to see any benefit from gene therapy.
Using parainfluenza virus, one of the viruses that causes common colds, the UNC scientists found that delivery of a corrected version of the CFTR gene to 25 percent of cells grown in a tissue culture model that resembles the lining of the human airways was sufficient to restore normal function back to the tissue.
“This is the first demonstration in which we’ve been able to execute delivery in an efficient manner,” says Ray Pickles, Ph.D., associate professor of microbiology and immunology at the UNC Cystic Fibrosis Research and Treatment Center. “When you consider that in past gene therapy studies, the targeting efficiency has been somewhere around 0.1 percent of cells, you can see this is a giant leap forward.”
“We discovered that if you take a virus that has evolved to infect the human airways, and you engineer a normal CFTR gene into it, you can use this virus to correct all of the hallmark CF features in the model system that we used,” Pickles said. For instance, the experiment improved the cells’ ability to hydrate and transport mucus secretions.
The next step is to work to ensure the safety of the delivery system. “We haven’t generated a vector that we can go out and give to patients now,” Pickles says, “but these studies continue to convince us that a gene replacement therapy for CF patients will some day be available in the future.”