Skin genetically engineered to destroy cocaine could prevent addiction

 作者:巩右鲫     |      日期:2018-01-12 04:18:43
Oliver Rüther/Plainpicture By Andy Coghlan People with cocaine addiction may soon be invited to test a pioneering new treatment that destroys the cocaine they take before it can hit the reward centres in their brain, using genetically engineered versions of their own skin cells. Currently, there are no approved treatments for cocaine addiction and many who do successfully kick the habit will ultimately relapse. Approximately 5000 Americans die each year from cocaine overdoses. The new therapy might help tackle the problem. Skin cells would be taken from recipients and equipped in the lab with an extra gene that constantly makes human butyrylcholinesterase (hBChE), an enzyme that rapidly destroys cocaine in the bloodstream. Then the cells would be multiplied into a clump called an organoid that doctors would implant permanently under the recipient’s skin. Ming Xu at the University of Chicago in Illinois and his colleagues have trialled the therapy in mice. Xu’s team’s results show that the prototype strategy worked exactly as hoped. Within 20 minutes, six mice with an active implant had practically eliminated a standard dose of cocaine injected into their tummies, a job that took six control mice almost 2 hours. And unlike the control mice, the treated mice didn’t get a “pleasure hit” in the brain from the neurotransmitter, dopamine. This absence of a “hit” also meant that unlike the controls, the treated mice didn’t go searching for more cocaine in standard tests to measure this behaviour, and didn’t preferentially visit previous sites where cocaine was accessible. They did, however, seek out more alcohol when it was made available to them, demonstrating that the treatment specifically targets cocaine addiction. Xu expects the treatment would be effective in people too. “It will work, like in mice, by highly efficiently degrading cocaine as soon as it enters the blood circulation so that little would reach the brain,” he says. “People addicted to cocaine would stop using it, and there would be no cocaine-induced relapses,” says Xu. “There are no methods approved by the US Food and Drug Administration for treating cocaine abuse, so it could be the first.” Almost all treated mice also survived huge doses of cocaine that killed controls. Xu gave treated and control animals doses of 40, 80, 120 and 160 milligrams of cocaine per kilo of body weight. All control animals died on the largest two doses, and half the controls on the 80-milligram dose. Xu’s team also tested prototype human versions of the organoids, made from foreskin cells of newborn baby boys. Like the mouse organoids, they produced the necessary enzyme continuously, for at least two months. “We’d like to move to clinical trials as soon as possible,” he says. Encouragingly, Xu says that some of the mice originally treated are still healthy, with active organoids, after six months, providing hope the treatment will be long-lasting in patients. He also says that similar grafts of patients’ own skin have been used without complications for decades to treat conditions such as burns and other skin disorders, which suggests the organoids wouldn’t be rejected. “I would expect this medication could prove effective when partnered with cognitive behavioural therapy to help people interpret and better cope with distressing cocaine craving,” says John Marsden, professor of addiction psychology at London’s Institute of Psychiatry. “It’s very encouraging that research in the US remains undaunted by the stubbornness of cocaine use disorder to respond to treatment, and I remain optimistic we’ll see an evidence-based medication.” Journal reference: Nature Biomedical Engineering, DOI: 10.1038/s41551-018-0293-z More on these topics: