Enzyme that ‘chews up fat’ could help develop addiction-free painkiller

17 May 2019

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Opioid addiction has become a crisis in some parts of the world, and now researchers have found what could lead to an addiction-free painkiller.

Some of the most effective painkillers are often a double-edged sword. While they might offer significant pain relief, some may also lead to the development of an addiction.

This has led researchers to try to discover new medication that can offer chronic pain relief, but allow for the patient to stop when they need to. Now, researchers at the University of Virginia have announced the discovery of an enzyme that “chews up fat” molecules to produce signals that control inflammation.

The naturally occurring enzyme – called diacylglycerol lipase-beta (DAGL) – is now a new drug target for reducing pain. Lead researcher Ken Hsu developed selective molecules that inhibit DAGL and reduce inflammation, similar to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs).

However, unlike NSAID inhibitors, DAGL provides relief without showing any addictive properties or gastrointestinal toxicity.

‘A new route to treating long-term pain’

“This could be a new route to treating long-term inflammation and pain without the side effects of toxicity and risk of addiction observed with current treatment options,” Hsu said. “Generally, if we block inflammation, we also affect the immune response. But we’re suggesting a different approach, one where we can stop inflammation without impacting the normal immune response.”

Publishing their findings to Cell Chemical Biology, they showed that DAGL was highly effective in reducing neuropathic pain and chemotherapy-induced peripheral neuropathy pain. Also, a new role for DAGL was found in dendritic cells – innate immune cells that not only control inflammation, but also produce T cells to fight infection.

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

Last year, another research team announced the development of a painkiller molecule that was as strong as morphine, but was not addictive.

Colm Gorey was a senior journalist with Silicon Republic