December 2, 2022

Chemistry teacher discovers possible non-addictive analgesic enzyme

Millions of Americans deal with pain daily, and the National Institute on Drug Abuse reports that approximately 1.7 million suffer from substance abuse disorders related to opioid use.

Researchers are looking for non-addictive chronic pain treatment options that have few or no negative side effects, and a University of Virginia chemistry professor may have found one.

Ken Hsu and his graduate student, Myungsun Shin, discovered an enzyme capable of producing chemical signals that control inflammation.

This enzyme, called diacylglycerol lipase-beta or DAGLb, could be used as a new drug to reduce pain.

During her postdoctoral training, Hsu developed selective molecules to inhibit DAGLb and reduce inflammation in a manner similar to aspirin and other nonsteroidal anti-inflammatory drugs, also known as NSAIDs.

He also found that these inhibitors could provide pain relief without gastrointestinal toxicity issues in preclinical models when used long term and without the addictive properties seen with opioids.

Hsu says studies at UVA in conjunction with Virginia Commonwealth University have shown that DAGLb inhibitors are highly effective in reducing different pain conditions, including neuropathic pain and chemotherapy-induced peripheral neuropathy.

He also discovered a new role for the enzyme in dendritic cells, which are a specialized type of immune cell that control inflammation and can activate the body’s ability to fight infection by stimulating T cells and creating a response. immune.

“We found that by blocking DAGLb we can stop inflammation without affecting immunity,” Hsu said. “This supports the idea that DAGLb is a viable target for long-term blockade of inflammation and pain without potentially compromising our immune system.”

His research program focuses on using chemistry to find new ways to modulate the immune system.

The results have been published in the online edition of the journal Cell Chemical Biology.