There are many potential reasons why skin might itch, but this annoying condition can significantly impact quality of life when it doesn’t go away. Scientists have had difficulty understanding what causes chronic itch, and while there are theories, there isn’t an effective treatment. New work reported in Science Translational Medicine may help change that.
In previous work, National Institute of Dental and Craniofacial Research (NIDCR) researcher Mark Hoon, Ph.D., and colleagues identified a receptor called Npr1. It was found on nerve cells in mouse spinal cord neurons and binds to a protein that’s been linked to itch. When the Npr1 receptor is bound to the protein, it helps cause the itch sensation. Blocking Npr1 then became a strategy in the search for drugs that can control chronic itch.
to develop drugs from what they identify eventually discover a therapeutic that can block Npr1, and potentially relieve chronic itchiness, researchers at the National Center for Advancing Translational Sciences (NCATS) and the NIDCR used a rapid screening technique to assess 86,000 compounds.
Hoon collaborated with NCATS scientist James Inglese, Ph.D., and his team to screen the molecules. They developed a variety of tests in their effort, and along with robot helpers, they narrowed the pool of potential drugs to about 1,400 compounds. Next, they created a new set of assays to identify the best candidates. A subset of fifteen molecules was eventually shown to stop the Npr1 receptor from functioning in both human and mouse cells. Following up in a mouse model, the scientists found that by block ing Npr1, scratching was reduced.
The investigators are continuing to search for more drugs that can stop Npr1 from binding its target and causing itchiness, and want to eventually develop drugs from what they identify.
"This is a proof-of-concept study and an important application of what NCATS does," Inglese said. "We wanted to show that by pharmacologically blocking the target receptor, the approach could be successful in finding a drug to treat chronic itch. Because it can take a long time to develop an ideal compound, the rationale behind the approach needs to be well-vetted."
Learn more about chronic itch from the video above, and why scratching an itch can make it worse from the following video.