A new therapy designed to prevent fentanyl overdoses has shown promise in an early study in monkeys.
Scientists have created an antibody that binds to the synthetic opioid fentanyl in the blood and stops a significant amount from reaching its target receptors in the brain. These receptors normally help to control how we perceive pain and experience emotions, as well as how we regulate our breathing. As a result, people who use fentanyl can experience difficulties breathing, and ultimately respiratory failure, if they take too much of the drug.
In the new monkey study, published Dec. 5 in the journal Nature Communications, a single dose of the antibody stopped fentanyl from triggering deadly reductions in breathing rate in four monkeys given high doses of the drug. This protective effect lasted almost a month.
The therapy also numbed the pain-relieving and euphoric effects of fentanyl, suggesting that it could be used to help people to stop taking the drug. However, the study didn't assess whether taking the antibody could trigger withdrawal symptoms in people who are dependent on fentanyl, so this still needs to be studied.
It's not yet known whether the new treatment would work in humans or how such a therapy could be made widely accessible to those at the highest risk of overdose. But if shown to be safe and effective, it could help combat the opioid overdose crisis currently gripping the U.S.
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"We're blocking not only the respiratory effects [of fentanyl], but notably, its pleasurable or reinforcing effects," Andrew Barrett, co-senior study author and chief scientific officer at Cessation Therapeutics, the company that developed the new antibody drug, told New Scientist.
"If we can block the high produced by fentanyl, gradually people will stop using it as they realize it is not doing anything," he said.
Fentanyl is a highly addictive, synthetic opioid that is approved by the U.S. Food and Drug Administration for use in medical settings as a painkiller and anesthetic. It mimics both the pain-relieving and pleasurable effects of natural opioids, such as heroin and morphine, that also target opioid receptors in the brain. However, fentanyl is 50 times stronger than heroin and 100 times more powerful than morphine.
Illicitly manufactured fentanyl has been a major factor driving the opioid overdose epidemic in the U.S. In recent years, the rate of drug overdose deaths involving fentanyl have more than tripled.
In the new study, the authors tested whether the new antibody, called CSX-1004, could prevent deadly respiratory failure in squirrel monkeys (Saimiri sciureus) given fentanyl.
Over 28 days, the authors injected untreated monkeys with fentanyl at increasingly higher doses, building up to what would be equivalent to a potentially deadly dose in humans. They found that this dosing regimen significantly reduced the primates' breathing rates, with the highest dose having the most extreme effect.
The researchers then repeated the regimen for another month, but this time treated the monkeys with a single dose of CSX-1004. The antibody counteracted the drug's effects, making it, on average, around 15 times less potent at reducing breathing rate across all doses of fentanyl.
There were no serious side effects of CSX-1004 treatment in the monkeys, and in a separate lab experiment, the antibody was even able to bind to at least 15 similar synthetic opioids, such as carfentanil.
The authors plan to test an injectable version of CSX-1004 in humans, New Scientist reported. A mid-stage clinical trial is also underway to test a similar antibody treatment that targets methamphetamine, the outlet reported.
There are many hurdles to overcome before this therapy could be rolled out in humans. For instance, it is very expensive to make antibodies like CSX-1004, and they have to be refrigerated, Dr. Thomas Kosten, a psychiatrist at Baylor College of Medicine who was not involved in the research, told the Los Angeles Times. It is also unclear whether health insurers would cover the cost of infusion treatment for patients with substance-use disorder, he said.
Nevertheless, the new findings represent a step toward bringing the drug to human patients.
This article is for informational purposes only and is not meant to offer medical advice.
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