CHICAGO, Sept. 22 (Xinhua) -- Researchers at the University of Chicago (UChicago) has developed a novel approach that is able to stifle the desire for cocaine and to protect against an overdose.
The approach has been tested in mice, according to the researchers, who also had three crucial mechanisms necessary to treat overdose and prevent addiction.
"We had an effective enzyme that can degrade cocaine with high efficiency," said Ming Xu, professor of anesthesia and critical care at UChicago. "We had CRISPR, a genetic tool that enabled us to introduce a gene of interest inside the cell without affecting other genes. And, most importantly we had technology to put genetically modified skin cells back into an immunocompetent recipient. That saved us a lot of trouble."
The enzyme, butyrylcholinesterase (BChE), can degrade cocaine. Because of its short half-life, injecting BChE directly into muscle tissue has a profoundly limited effect.
To make long-lasting BChE, the researchers collected primary epidermal basal progenitor or stem cells from newborn mice. They used CRISPR to deliver engineered human BChE to the cells. Then they used a technique to prepare skin organoids and transplant them back to the donor animals, where they act as a depot for robust expression and secretion of hBChE into the blood stream. This efficiently protected the mice from cocaine-seeking and cocaine-induced relapse. It even prevented the death of mice exposed to uniformly lethal doses of cocaine.
Cutaneous gene therapy can be used as a "safe and effective way for treatment of non-skin diseases, including drug abuse, a scenario that has not been explored before," the researchers note. "We demonstrated key evidence that engineered skin transplants can efficiently deliver hBChE in vivo and protect against cocaine-seeking and overdose."
These stem cells were well tolerated by the injected mice. The grafted skin cells exhibited normal epidermal stratification, proliferation and cell death.
The skin-derived expression of hBChE in host mice with intact immune systems was stable for more than 10 weeks without significant decrease in hBChE. This suggests that the skin environment may limit any potential immune reaction toward hBChE.
The oldest mice in this study are now 12 months old and healthy. "Taken together, our results show promise of cutaneous gene therapy as a safe and cost-effective therapeutic option for cocaine abuse in the future," the researchers said.
For cocaine addicts or those prone to cocaine abuse, this approach could reduce drug-seeking and protect against cocaine overdose, potentially making them "immune" to further cocaine abuse. This skin cell-based approach can potentially be used to treat alcohol, nicotine and opioid abuse and co-abuse.
About five percent of young adults in the United States, roughly 1.7 million people aged 18 to 25, have used cocaine at least once, according to the 2015 National Survey on Drug Use and Health. More than 900,000 Americans are dependent on, or abuse this drug.
