New understanding of exaggerated mucous production and secretion in cystic fibrosis

A London, Canada scientist studying cystic fibrosis (CF) has successfully corrected the defect which causes the overproduction of intestinal mucous in mice.

This discovery by Dr. Richard Rozmahel, a scientist with the Lawson Health Research Institute, affiliated with The University of Western Ontario, has clear implications to understanding and treating this facet of the disease in humans. CF is a fatal, genetic disease characterized by an overproduction of mucous in the lungs and digestive system.

Rozmahel and his colleagues are identifying secondary genes that could contribute to CF, and measuring their impact on the disease. More specifically, they are investigating the potential of a gene found in mice, mCLCA3, which is similar to one in humans that exhibits abnormal levels in CF. The mCLCA3 gene is expressed by cells that produce and secrete mucous.

The researchers discovered that mCLCA3 plays an important role in the property of mucous, thereby allowing it to be cleared rather than result in the blockages that underlie CF. By correcting the abnormal levels of mCLCA3 in CF mice they were able to overcome the mucous lesions. Whereas CF mice normally do not survive more than 4 weeks as a consequence of the mucous disease, the animals where mCLCA3 levels were corrected could live a normal lifespan.

"It's my hope to understand what is causing the exaggerated mucous production and secretion in CF patients," says Dr. Rozmahel. "From there, we can figure out ways to correct it."

Rozmahel is a Lawson scientist at the Children's Health Research Institute and the London Regional Cancer Program at the London Health Sciences Centre. He's also an associate professor of Biochemistry, Pediatrics and Oncology at the Schulich School of Medicine & Dentistry at The University of Western Ontario.

CF is a chronic inherited disease affecting 70,000 children and adults worldwide. In the late 1930's, CF was usually recognized only after a child had died, often as a result of malnutrition or pneumonia. Medical awareness of CF has increased tremendously over the years, and doctors are now able to diagnose most patients within the first year of life. Thanks to advances in research and clinical care, growing numbers of children with CF are surviving into adulthood, compared to the 1960's, when most patients died by age four. Now the median age of survival is 37 years.