Treatments for asthma, allergies to become safer

A missing link between the body’s biological clock and sugar metabolism system has been discovered, which may help avoid the serious side effects of drugs used for treating asthma, allergies and arthritis.

Scientists at the Salk Institute for Biological Studies found that proteins that control the body’s biological rhythms, known as cryptochromes, also interact with metabolic switches that are targeted by certain anti-inflammatory drugs.

The finding suggests that side effects of current drugs might be avoided by considering patients’ biological rhythms when administering drugs, or by developing new drugs that target the cryptochromes.

“We knew that our sleep and wake cycle are tied to when our bodies process nutrients, but how this happened at the genetic and molecular level was a complete mystery,” said Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory, who led the research team.

“Now we’ve found the link between these two important systems, which could serve as a model for how other cellular processes are linked and could hold promise for better therapies,” he explained.

Glucocorticoids are steroid hormones that occur naturally in the body and help control the amount of sugar in a person’s blood, so that nutrient levels rise in the morning to fuel daily activities and fall again at night. They function in cells by interacting with glucocorticoid receptors, molecular switches on the outside of the nucleus, which Evans first discovered in 1985.

In their new study on mouse cells, Evans and his colleagues made the surprising discovery that cryptochromes also interact with glucocorticoid receptors, helping to regulate how the body stores and uses sugar.

“We found that not only are the crytopchromes essential to the functioning of the circadian clock, they regulate glucocorticoid action, and thus are central to how the clock interacts with our daily metabolism of nutrients,” stated Katja A. Lamia, an assistant professor at The Scripps Research Institute and former post-doctoral researcher in Evan``s laboratory at Salk.

By taking into account the daily rise and fall of cryptochrome levels, the scientists say, doctors might be able to better time administration of glucocorticoid drugs to avoid certain side effects related to sugar metabolism.

The study was published last week in Nature.