A radical gene therapy for drug addiction has been shown to dampen down cravings for cocaine and protect against overdoses of the substance that would normally be lethal. 
 
 The therapy uses implants of stem cells which have been genetically engineered to release a powerful enzyme that removes the class A drug from the bloodstream. 
 
 Tests in the lab showed that mice fitted with the implants lost their appetite for cocaine and survived massive overdoses of the drug that killed 100% of untreated animals. 
 
 The work has raised hopes for a long term treatment for addiction that works by clearing drugs from the body as soon as they are injected, inhaled or ingested. The therapy would effectively make addicts immune to the substances. 
 
 Lead researcher Ming Xu, a professor of anaesthesia and critical care at the University of Chicago, said the approach was “highly efficient and specific for eliminating cocaine.” 
 
 “Compared to other gene therapies, our approach is minimally invasive, long term, low maintenance and affordable. It’s very promising,” he told the Guardian. 
 
 Scientists have known for decades that an enzyme found in blood plasma called butyrylcholinesterase, or BChE, destroys cocaine by breaking it down into harmless byproducts. But the enzyme is not particularly fast-acting and does not linger in the bloodstream long enough to help those addicted to the drug. 
 
 To create their new therapy, the Chicago researchers rewrote the DNA in mouse skin stem cells to make them churn out a modified form of BChE that is 4,400 times more potent than the natural enzyme. The scientists reasoned that clumps of these engineered cells, called organoids, could be implanted under the skin, where they would release the cocaine-busting enzyme into the blood. 
 
 Tests in mice suggest the concept might work. Writing in the journal Nature Biomedical Engineering on Monday, Xu and his colleagues describe how they implanted genetically engineered organoids under the skin of several mice. Blood tests showed that the animals had consistently high levels of BChE for at least 10 weeks. As a result, the mice sought cocaine less than untreated animals, and were able to withstand normally fatal overdoses of the drug, up to 160mg per kg of bodyweight, the equivalent of 12g in a 75kg person. Estimated lethal doses of cocaine vary wildly in humans, but can be as low as 0.05g when taken nasally. 
 
 Xu believes the experimental therapy has the potential to become the first intervention approved for the treatment of cocaine addiction. Lab studies suggest that similar implants for humans could release BChE for 20 to 30 years, he said, and so potentially protect addicts for decades. “We have not observed obvious side effects, but will study them carefully,” Xu said. 
 
 Deaths from cocaine in England and Wales rose for the sixth consecutive year in 2017 with 432 lives lost to the drug, according to a report from the Office of National Statistics. In July, the Metropolitan police commissioner, Cressida Dick, criticised middle class cocaine users for fuelling the domestic drug trade. According to the latest crime survey for England and Wales, cocaine was used by an estimated 875,000 people in 2017-18, the highest number in a decade. 
 
 Though more work is needed before the cocaine-blocking therapy can be trialled in humans, Xu believes the approach has the potential to make drug users immune to cocaine and protect them from fatal overdoses. The team is working on similar genetically-engineered cells to treat alcohol and nicotine addiction, and soon expect to start research on a therapy for opioid addiction, Xu said. ||||| Oliver Rüther/Plainpicture 
 
 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. 
 
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 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. 
 
 No cocaine-induced relapses 
 
 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 
 
 Read more: The love drug that could draw people away from any addiction ||||| Addiction to any drug – be it alcohol, tobacco, opioids or illicit drugs, like cocaine – is a chronic disease that causes a compulsive drug-seeking behavior individuals find difficult or impossible to control even when they are aware of the harmful, often deadly consequences. 
 
 Long-term use changes the structure of brain regions linked to judgment, stress, decision-making and behavior, making it increasingly difficult to ignore drug cravings. 
 
 I am a postdoctoral researcher in the laboratory of Ming Xu at the University of Chicago, where we study addiction, with a goal of finding an effective cure. In a paper in Nature Biomedical Engineering, we describe a new approach, which we developed and tested, that blocks cocaine-seeking in mice and actually protects them from high doses that would otherwise be deadly. 
 
 How can gene therapy stop addiction? 
 
 Present in human liver and blood is a natural enzyme called butyrylcholinesterase, which we abbreviate as BChE. One of this enzyme’s jobs is to break down, or metabolize, cocaine into inactive, harmless components. In fact, there is even a mutant human BChE (hBChE), which was genetically engineered to greatly accelerate the metabolism of cocaine. This super mutant enzyme is expected to become a therapy for treating cocaine addiction. However, delivering the active enzyme to addicts by injection and keeping this enzyme functioning in living animals is challenging. 
 
 So instead of giving the enzyme to the animals, we decided to engineer skin stem cells that carried the gene for the BChE enzyme. This way the skin cells would be able to manufacture the enzyme themselves and supply the animal. 
 
 In our study, we first used the gene-editing technique CRISPR to edit the mouse skin stem cells and incorporate the hBChE gene. These engineered skin cells produced consistent and high levels of the hBChE protein, which they then secreted. Then we grew these engineered stem cells in the lab and created a flat layer of skin-like tissue which took a few days to grow. 
 
 Once the lab-grown skin was complete, we transplanted it into host animals where the cells released significant quantities of hBChE into blood for more than 10 weeks. 
 
 With the genetically engineered skin graft releasing hBChE into the blood stream of the host mice, we hypothesized that if the mouse consumed cocaine, the enzyme would rapidly chop up the drug before it could trigger the addictive pleasure response in the brain. 
 
 ‘Immunizing’ against cocaine 
 
 Cocaine works by elevating dopamine levels in the brain which then result in feelings of reward and euphoria, which trigger a craving for more of the drug. 
 
 The animals that received the engineered skin graft were able to clear injected quantities of cocaine faster than control animals. Their brains also had lower levels of dopamine. 
 
 Moreover, the skin grafts of hBChE-producing cells can effectively decrease the rate of lethal overdoses from 50 percent to zero when the animals were injected with a high, potentially lethal, dose of cocaine. When animals were given a lethal dose, all the control animals died while none of the animals that received the engineered skin perished. It was as if the enzyme produced by the skin graft had immunized the mice against a cocaine overdose. 
 
 We then assessed whether hBChE-producing cells can protect against development of cocaine-seeking. We used mice that were trained to reveal their preference for cocaine by spending more time in a cocaine-rich environment. Under the same dosage and training procedures, normal animals acquired preference to cocaine, whereas host animals with the skin graft showed no such preference, indicating skin graft of the hBChE-cells efficiently blocks the cocaine-induced reward effect. In a similar way, skin-derived hBChE efficiently and specifically disrupts recurrence of cocaine-seeking after 25 days of withdrawal. 
 
 To test whether this gene therapy approach will work in humans, we grew human skin-like tissue from primary skin stem cells that were genetically edited by CRISPR to allow hBChE production. 
 
 We were encouraged to see that engineered human epidermal cells produced large quantities of hBChE in cells cultured in the lab and in mice. This suggests the concept of skin gene therapy may be effective for treating cocaine abuse and overdose in humans in the future. 
 
 Adapting this approach for humans could be a promising way for blocking addiction. But first we must have sufficient evidence that it works well with few side effects. Likewise, engineering skin cells with the enzymes that degrade alcohol and nicotine could be an effective strategy for curbing addiction and abuse of these two drugs as well.
– Could a skin graft help cocaine addicts get clean? Scientists at the University of Chicago say their novel approach has worked in mice, reports New Scientist. And if this translates to humans, it could be a game changer, though the remedy is specific to cocaine addiction. In a new study in Nature Biomedical Engineering, the researchers explain that their work revolves around an enzyme we naturally produce called BChE. The enzyme is unique in that it's a cocaine killer—it essentially destroys any cocaine it comes across in the bloodstream—but the body produces too little of it to be of use for addicts. Solution? The scientists say they can take skin cells from people, arm them with a jacked-up version of BChE, and then implant them back under the recipient's skin. The process, taking advantage of the gene-editing technique CRISPR, produced strong results in mice. "Compared to other gene therapies, our approach is minimally invasive, long term, low maintenance, and affordable," lead researcher Ming Xu tells the Guardian. "It's very promising." In the study, mice that received the implants eliminated a standard dose of cocaine from their bodies in 20 minutes, versus two hours for the control mice. Crucially, the first group didn't get a "pleasure hit" from the drug, either, per New Scientist. As the Guardian puts it, the treatment essentially made the mice immune to cocaine. What's more, all the mice with the implants survived doses of cocaine that killed the control mice. "Adapting this approach for humans could be a promising way for blocking addiction," another researcher writes at the Conversation, and she lays out the next steps underway toward that goal. (Humans aren't the only creatures having trouble with cocaine.)