It has been more difficult than scientists had hoped to turn knowledge about the basic causes of cystic fibrosis (CF) into effective treatments for the disease. But researchers are still hard at work, and a group from Carolina recently published a finding that may lead to a new avenue in pursuing treatment.

In 1989, scientists discovered the gene, called CFTR, that, when defective, causes CF. This finding,which was seen as a breakthrough, has been useful in testing carriers of CF and in gene therapy trials. But CFTR hasn't answered all the questions about CF. Researchers have been unsure how the defective gene causes the clogged airways and chronic, debilitating infections of CF. For one thing, researchers know that CF patients' inability to clear mucus from their lungs has to do with chloride, a component of salt. But they haven't known whether patients' lungs contain too much salt or not enough.

Now, they do.

"The answer pretty unequivocally is that there's too little salt," said Richard C. Boucher, professor of medicine and director of Carolina's Cystic Fibrosis/Pulmonary Research and Treatment Center. A report on the finding appears in the July 20 issue of the journal Molecular Cell. Besides Boucher, authors are research associates Robert Tarran (the lead author), Maryse Picher, and Andrew J. Hirsh; Barbara Grubb, associate professor of medicine; and C. William Davis, research associate professor of cell and molecular physiology. David Parsons, of Women's and Children's Hospital in Adelaide, Australia, also contributed to the work.

The salt question has been difficult to study because the layer of salt and water that coats airways in the lung is only about a millionth of an inch thick, Boucher said. And, studying human lungs isn't practical.

Instead, the Carolina group studied genetically engineered CF mice, bred at the University, that have the same problem with salt transport in their noses as CF patients do with their lungs. The researchers measured this problem electrically in the mice with a device similar to an electrocardiograph machine. By examining the nasal tissue itself, the scientists found that the abnormal electrical activity was associated with disease--the tissue contained too many mucous-secreting cells and was chronically inflamed. "The question then was, what was the link between abnormal electrical activity and diseased airways--too little salt or too much salt?" Boucher said.

The group answered that question by measuring the amount of water on the mice's airway surfaces. Salt holds water on these surfaces. The CF mice's airway surfaces contained less water than such surfaces in normal mice. "Since salt holds water on these surfaces, that means that the CF mice have less salt," Boucher said.

Using cultured human airway cells from CF patients, the group found that adding salt back to the cells promoted clearance of the sticky mucous that is the problem in CF lung disease. The next step, Tarran said, is finding substances that will add salt back to the cells and that will be long-lasting inside actual lungs. Unfortunately, many of the compounds used now in CF drug trials are rapidly cleared from the lungs.

Another group at Carolina is ensuring that such findings can be more easily put to use. The Cystic Fibrosis Foundation established the CF National Bioinformatics Center at the University to help scientists share rapidly growing genetics data. Merging biology and computer science, the center is a collaboration between Carolina, InforMax Inc. and the CF Foundation. The center, led by director David Fenstermacher, assists with data analysis and allows scientists around the world to share data through the Internet.

Editor's note: Richard C. Boucher was named one of the top ten researchers funded by the National Institutes of Health (NIH) in 2000, receiving $5.1 million in NIH grant funding for cystic fibrosis research that year.