In a crucial step toward finding a cure for the nation's most common inherited fatal disease, scientists say they have repaired cells with the genetic defect that causes cystic fibrosis.
In separate but complementary studies released Thursday, two research teams used genetic engineering techniques to fix the disease-causing problems in cells taken from people suffering from cystic fibrosis.The cells were only corrected in the test tube and were not returned to the patients. Any efforts to use gene therapy to treat cystic fibrosis are likely years away because the approach first must be tested in animals, and researchers also must figure a way to get the genes into patients' lungs, possibly through inhalation.
"This is another step in the direction of offering cystic fibrosis patients treatment, but it is not treatment. On the other hand, patients should take hope and feel good about this achievement. It could have taken longer and been more complex," said Dr. Francis Collins of the University of Michigan in Ann Arbor, one of the leaders of the research.
Currently there is no treatment to prevent or directly attack cystic fibrosis, a disease in which thick mucus clogs the lungs and leads to life-threatening infections. About one of every 2,000 white babies is stricken by cystic fibrosis, and most patients die before they reach age 40.
Robert Dresing, president of the Cystic Fibrosis Foundation, said, "There are major steps to achieve before human gene therapy, but this research is a milestone in the drive to cure cystic fibrosis."
Although their approaches varied slightly, both teams of scientists used a virus to insert a normal copy of the cystic fibrosis gene into cells taken from diseased patients and grown in laboratory dishes. After receiving the healthy gene, the cells appeared to function normally. he achievement comes about a year after the discovery of the genetic flaw that causes the vast majority - about 70 percent - of cystic fibrosis cases.
At that time, researchers speculated that the protein that the gene codes helped transport salt out of cells. Chloride, which is a component of salt, regulates cells' water levels, and upsetting that balance appears to be what causes the mucus of cystic fibrosis patients to thicken.
In a study published in the journal Cell, a team from the University of Michigan, the University of Alabama at Birmingham and The Hospital for Sick Children in Toronto used a mouse virus that had been rendered harmless to put normal genes into cells taken from a pancreas tumor in a cystic fibrosis patient.
Before the gene implant, the pancreatic cells did not allow salt to properly cross their membranes. After the procedure, those cells transported salt as effectively as cells taken from the airways of healthy people, a change that lasted at least two months and should be capable of producing normal mucus, researchers said.
That team is now working on implanting normal genes into cells from the airways of people with cystic fibrosis because respiratory problems, not pancreas problems, are the major killers of such patients. The pancreas cells were used in the first test because they were easier to grow.
Meanwhile, in a study to be published next week in the British journal Nature, researchers from the University of Iowa in Iowa City, Genzyme Corp. of Framingham, Mass., and Tufts University in Boston used a cowpox virus to insert normal genes into airway cells taken from cystic fibrosis patients. The corrected cells functioned normally, while comparison cystic fibrosis cells that received an extra copy of the defective gene still did not work properly.
"These results suggest attempts to correct the defect in a cystic fibrosis person is realistic. But there could be an immense amount of work before we can achieve that," said Michael Welsh of the University of Iowa, a co-author of the Nature article.
Dr. Gary Cutting, a cystic fibrosis researcher at Johns Hopkins School of Medicine in Baltimore, said he was impressed with the new findings. "This is an exciting step toward a potentially real treatment for the disease and perhaps a cure," he said.
The work not only opens the door to gene therapy, Cutting said, but also advances the effort to develop drugs that might replace the defective protein or offset its harmful effect.