Discovery could improve the treatment of cystic fibrosis

Researchers studying the effects of a long-standing treatment for cystic fibrosis have discovered a new potential target for drugs to treat this disease, which has no curative treatment and usually reduces by several decades the lives of patients.

The research, a collaboration between the University of Saskatchewan in Canada and UC Berkeley, is based on a unique method developed by Canadian researchers to measure fluid secretion in the lungs. Cystic fibrosis, a genetic disorder, is characterized by thick, viscous mucus that obstructs the airways and causes the buildup of bacteria, resulting in frequent infections that damage the airways. It is caused by a defective ion channel in the cells of the whole body, thus preventing cells lining the airways from secreting enough fluid to thin the mucus.

"For over 20 years, doctors have been treating CF patients by asking them to inhale the fog of a concentrated salt solution to increase the amount of fluid lining the surface of the airways," he said. Terry Machen, Emeritus Professor of Molecular and Cell Biology, Berkeley. "This facilitates the removal of thick mucus and bacteria."

Hypertonic saline was also thought to function by pbadively aspirating the fluid from the tissue spaces in the respiratory tract by osmosis.

The new experimental technique has shown that this is true in pigs with cystic fibrosis, but the saline solution increases the secretion of active fluid by the epithelial cells lining the airways. This is probably due to other ion channels than the defective one, called the transmembrane conductance regulator of cystic fibrosis, or CFTR.

"The game changer that we have discovered is that only about half of the liquid production at the surface of the airways is due to the osmotic process.The other half of the fluid secretion comes from the salt spray that stimulates the Action of airway neurons, "said Julian Tam, a pulmonologist at the University of Saskatchewan College of Medicine (USask) and director of the Adult Cystic Fibrosis Clinic in Saskatoon, which has directed research with Juan Ianowski, physiologist at USask College of Medicine.

"These results indicate that the responses of CF patients to therapeutic drugs could be improved by identifying, characterizing and controlling the non-CFTR ion channels and the nerves controlling these channels, which appear to mediate the active response to hypertonic saline in the lungs, "says Machen. "The results of this study are consistent with our long-held belief that the pathology of CF results solely from the loss of CFTR channel function and that treatments that facilitate or restore this function will be clinically beneficial."

The team published its study on January 25 in Scientific reports.

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University of California, Berkeley