Scientists identify a potential approach to a chronic problem

Chronic itching goes beyond a simple annoyance; this can greatly affect the quality of life of a person. Although scientists have clues about its causes, effective treatments have been difficult to achieve.

Now, using a technique called quantitative high-throughput screening to screen over 86,000 compounds at the same time, researchers at NCATS and the National Institute of Dental and Craniofacial Research (NIDCR) report a new strategy that could eventually help alleviate chronic itching. They showed that blocking a receptor, or docking station, on the surface of neurons in the spinal cord of mice and humans could be the key to success.

Several years ago, Mark Hoon, Ph.D., and his colleagues at NIDCR discovered a receptor, Npr1, on mouse spinal cord neurons for an itch-related protein. The protein enters Npr1 as a key in a lock, helping to activate the itchy feeling. Npr1 appeared to be a potential target for medications to stop the itch.

Hoon contacted James Inglese, Ph.D., a scientist at NCATS, and his team to help them identify compounds that could block Npr1 activity. The researchers developed a series of tests and tests and used robots to screen compounds in human cells. They discovered about 1,400 molecules that deserved closer examination. They then developed additional tests to reduce the list to 15 compounds. They showed that a subset of these compounds could prevent the human and murine versions of the receptor from functioning. A follow-up study in mice showed that receptor blockade reduced scrapes.

Next, scientists will investigate more candidate compounds and determine how they block Npr1. They hope the results will help them select the compounds to study and chemically modify as potential anti-itch medications. Hoon, Inglese and their colleagues reported online results on July 10 Translational medicine science.

"This is a concept validation study and an important application of what the NCATS does," Inglese said. "We wanted to show that by pharmacologically blocking the target receptor, the approach could make it possible to find a drug to treat chronic itching.Because it sometimes takes a long time to develop an ideal compound, its logic must be carefully checked. "