Clearing the airways in cystic fibrosis

By manipulating the machinery used by our cells for quality control, researchers from the University of Pittsburgh have found a way to restore the function of cystic fibrosis (CF) airway cells. This could significantly reduce the sticky mucus that plugs the lungs of CF patients, which leads to antibiotic-resistant infections and untimely death. The study, appearing in the September 2008 print issue of The FASEB Journal (http://www.fasebj.org), is significant because it shows a new way to manipulate the cellular quality controls of all sorts of proteins which play a role in conditions ranging from aging to cancer. "Our hope is that this work will provide new approaches for recovering function from the protein whose inability to fold and function properly compromises the quality of life and life expectancies of people with CF," said Raymond Frizzell, senior author on the study. The researchers say, however, that it is too early to tell exactly what other conditions this technique will affect.

Most people do not realize that when our bodies produce proteins, they sometimes make mistakes. Similar to what happens on assembly lines, these mistakes are rejected and prevented from being used. In most people with CF, however, defective (i.e., mutant) CFTR proteins made by airway epithelial cells could actually be beneficial if they were allowed to reach their final destination at cell surfaces. To help these mutant proteins (the {DELTA}F508 CF gene mutation) reach cell surfaces, researchers developed a "decoy," made up of only a portion of the complete mutant protein, which is rejected instead. In airway epithelial cells taken from CF patients, the "distracted" airway cells allowed the complete {DELTA}F508 CFTR protein to evade the quality control mechanisms that would have normally destroyed it.

"Since this pivotal discovery of the CF gene nearly 20 years ago, researchers have made more progress toward a cure than they had in thousands of years before," said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. "People with cystic fibrosis now live longer than once ever thought possible, and basic science breakthroughs like this one keep the trend ever upward."

According the U.S. Cystic Fibrosis Foundation, cystic fibrosis affects about 70,000 people worldwide. It is caused by a defective gene and its protein product, which causes the body to produce very thick and sticky mucus. This mucus clogs the lungs and leads to life-threatening lung infections. It also blocks enzymes from the pancreas that needed to break down and absorb food. Sixty years ago, few children with cystic fibrosis lived to attend elementary school. Today, the projected median survival age is 37.

Source: Federation of American Societies for Experimental Biology