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Salk discovery may lead to safer treatments for asthma, allergies and arthritis

asthma illustration

Illustration: Jamie Simon, Salk Institute for Biological Studies.

Glucocorticoids are steroids that occur naturally in the body and help control the amount of sugar in a person's blood. They also play a role in regulating inflammation and are used as anti-inflammatory drugs for diseases caused by an overactive immune system, such as allergies, asthma and rheumatoid arthritis. And they are used to treat inflammation in cancer patients. Because of their role in sugar metabolism, however, they can disrupt a person's normal metabolism, resulting in dangerous side effects, including excessive blood sugar levels, insulin resistance and diabetic complications.

Now researchers in the lab of Ronald Evans may have found a way around these side effects. In a study published in Nature, the team reported that proteins controlling the body's biological clock, known as cryptochromes, also interact with metabolic switches that are targeted by certain anti-inflammatory drugs.

"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," says Evans. "The link we've found between our biological clock and metabolism serves as a model for how other cellular processes communicate with each other and could hold promise for better therapies."

Cryptochromes were previously known for their function in the biological clock, serving to slow its activity and signal our biological systems to wind down each evening. With the morning sun, they stop inhibiting the clock's activity, helping our physiology ramp up for daytime activities. In their study, Evans and his colleagues made the surprising discovery that beyond the "clock," cryptochromes also interact with glucocorticoid receptors that help to mobilize sugar production in the body. 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.

It could have important implications for treatment of autoimmune diseases and cancer, enabling doctors to better time administration of glucocorticoid drugs. It also raises the possibility of developing new anti-inflammatory drugs that avoid some side effects altogether by targeting cryptochromes instead of the glucocorticoid switches. More broadly, Evans says, the study may help explain the connection between sleep and nutrient metabolism in our bodies, including why people with jobs requiring night work or erratic hours are at higher risk for obesity and diabetes.