Danforth Center researchers hope enzyme leads to cleaner, cheaper opioid antidotes

Researchers at the Donald Danforth Plant Science Center in Creve Coeur have discovered an enzyme they say could decrease the toxicity and cost of producing drugs to reverse the effects of opioids.

By exploring wastewater associated with the processing of opium poppy, researchers Megan Augustin and Toni Kutchan found a bacteria and enzyme that aids in the creation of thebaine, which is used in the opioid antidote naloxone. Naloxone is commonly marketed under the brand name Narcan.

“Enzymes can do the chemistry that chemists can only dream of,” Augustin said, “and if we could start to really promote the use of enzymes in our processes, we are going to greatly reduce our impact on the environment.”

Current production techniques to access thebaine and create naloxone utilize toxic and synthetic chemicals, which produce toxic waste. The process can be harmful to chemists and the environment, Kutchan said.

The use of the naturally occurring enzyme would mean a greener — and cheaper — process, according to Kutchan.

“If the use of this enzyme were to be incorporated, we would reduce the number of steps and we would reduce the problem of treating some of the waste that comes out of production,” Kutchan said. “That has to be cost-saving.”

With the rate of drug overdose deaths in the U.S. hitting an all-time high in 2017, more affordable solutions to opioid overdoses are in high demand. The 2019 Commonwealth Fund health scorecard reported that deaths from drug overdose now surpass suicide or alcohol. There was a 115% increase from 2005 to 2017 in deaths due to overdose, and opioids accounted for about 68% of overdose deaths in 2017, according to the Centers for Disease Control.

“The idea is to make sure all first responders always have with them the antidote to opiate overdose to save lives, and right now it’s a cost problem,” Kutchan said.

The FDA announced in January that it hopes to streamline the process of purchasing naloxone by allowing it to be sold over the counter. Narcan, a nasal spray, is currently used nationwide in emergency rooms.

The two-pack nasal spray retails at about $125, CNBC reported in January, while a generic version is $40. Narcan’s producer, Kaleo, has an injection listed at $4,100 and plans on releasing a generic version this year for $178.

Kutchan said the enzyme could possibly be used in the process of creating naloxone, or create a new drug in itself. Either way, she said, its use would likely be more cost-effective, in addition to offering environmental benefits.

“If it can be made more efficiently and less expensive, maybe we can increase the availability of what’s an important treatment drug for opiate overdose as we as a country get the problem of addiction under control,” Kutchan said

They have filed a patent for the enzyme and are searching for an industrial partner to “convert this from a lab discovery to a commercial process,” Kutchan said. The researchers said the use of the enzyme can also be transferred into processes for medication with other diseases, like Alzheimer’s Disease, and possibly contribute to drug discovery.

“I specifically want to promote doing things new and different … instead of always doing things the old way,” Augustin said.

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