It has been shown that radical gene therapy for drug addiction reduces the craving for cocaine and protects against overdoses of the substance that would normally be fatal.
The therapy uses stem cell implants that have been genetically engineered to release a powerful enzyme that removes the class A drug from the bloodstream.
Tests in the laboratory showed that mice with the implants lost their appetite for cocaine and survived huge overdoses of the drug that killed 100% of the untreated animals.
The work has generated hope for a long-term treatment of addiction that works by removing medicines from the body as soon as they are injected, inhaled or ingested. The therapy would effectively make addicts immune to the substances.
Principal investigator Ming Xu, professor of anesthesia and critical care at the University of Chicago, said the approach is "very efficient and specific for eliminating cocaine."
"In comparison with other gene therapies, our approach is minimally invasive, long-term, low-maintenance and affordable, and promising," he told the Guardian.
Scientists have known for decades that an enzyme found in the blood plasma called butyrylcholinesterase or BCHE destroys cocaine by breaking it down into harmless by-products. But the enzyme is not working very fast and does not stay in the bloodstream long enough to help the addicts to the drug.
To create their new therapy, the Chicago researchers rewrote the DNA in mouse skin stem cells to make them 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-degrading enzyme in the blood.
Tests in mice suggest that the concept might work. In the journal Nature Biomedical Engineering on Monday, Xu and his colleagues describe how they implant genetically engineered organoids into the skin of different mice. Blood tests showed that the animals consistently had a high BChE level for at least 10 weeks. As a result, the mice sought less cocaine than untreated animals and were able to withstand normally fatal overdoses of the drug, up to 160 mg per kg body weight, the equivalent of 12 g in a 75 kg person. Estimated lethal doses of cocaine vary enormously in humans, but can be as low as 0.05 g when taken by mouth.
Xu believes that experimental therapy has the potential to become the first intervention approved for the treatment of cocaine addiction. Lab studies suggest that similar implants for people could release BChE for 20 to 30 years, he said, and possibly protect addicts for decades. "We have not observed any obvious side effects, but will study them carefully," Xu said.
Mortality 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 police commissioner of Metropolitan, Cressida Dick, criticized middle-class cocaine users for the stimulation of domestic drug trafficking. According to the most recent crime survey for England and Wales, cocaine was used by an estimated 875,000 people in 2017-18, the highest number in a decade.
Although more work is needed before cocaine-blocking therapy can be tried 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 expects to soon start research into opioid addiction therapy, Xu said.