A New Angle on CF
by Lynn Thomasson
It's a battle against congestion. The enemy, mucus, is thicker and stickier than that found in any normal cold or flu and maintains a stronghold in the victim's lungs. For the approximately 30,000 Americans living with cystic fibrosis (CF), breaching this stronghold is a lifelong fight.
While the genetic disorder affects various parts of the body, including the digestive system and reproductive system, it is usually a crippling lung disease that kills. But researchers at the Cystic Fibrosis/Pulmonary Research and Treatment Center at Carolina are fighting back. They've created a new weapon to battle the lung disease and found answers along the way.
In an article published in the May 2004 issue of Nature Medicine, several researchers from Carolina and a colleague from Michigan State University answer a key question in understanding the disease that has stumped scientists for years. What causes the fatal lung disease?
In a word, dehydration. "We now understand that adequate hydration is critical for normal lung defense from bacteria," says Marcus Mall, the study's lead researcher.
CF causes the lung to absorb an excessive amount of salt, subsequently stripping water from airway surfaces. Without enough water to lubricate lung surfaces, the cilia hairs, which ordinarily move mucus out of the lungs, stop working. Stuck in the lungs, the mucus develops into a breeding ground for a myriad of infectious bacteria.
Twelve years ago, UNC-Chapel Hill scientists genetically modified the first mouse with the CF gene. Surprisingly, the mouse did not show any signs of the characteristic CF lung disease. The researchers proposed a multitude of theories to explain the cause of the lung disease, from mucus overproduction to malfunctioning cilia. Yet when applied to a mouse model, none of these factors produced the crippling lung disease.
The Carolina team tried testing a different theory — that dehydrated airway surfaces result in lung disease. They genetically modified the lungs of a live mouse to absorb extra salt and water, and a CF-like lung disease resulted. The new mouse model doesn't contain the CF genetic disorder, simply its characteristic lung disease.
And it's already changing how scientists conduct research. "We had about forty different people already contact us wanting to use these mice in their research," says Richard Boucher, director of the Cystic Fibrosis/Pulmonary Research and Treatment Center.
Previous CF research relied on human tests and cell cultures. Both Boucher and Mall agree that the new mouse model will speed drug development by allowing scientists to go to an in vivo model faster. Boucher says, "You can do an experiment on a mouse in four to six weeks which would take two and a half years to do on people."
The benefits of a mouse model of dehydrated airway surfaces extend beyond
CF. Mall points out that this model can be used to research other lung
diseases such as chronic bronchitis and asthma. "The next step is
that we will use this model to test new therapeutic strategies that we
think could work in preventing this disease," Mall says.
Barbara Grubb and Wanda O'Neal of Carolina and Jack Harkema of Michigan State University also participated in this project.
Lynn Thomasson is a sophomore majoring in biochemistry at Carolina.
