Researchers studied whether skin gene therapy could reduce cocaine-seeking behaviors.
The drug addiction “epidemic” claims tens of thousands of lives each year in America, but until now there has been little talk of ways to immunize people against substance use disorder.
However, in the future that may be possible, according to new research that found that skin grafting might be used to protect people from cocaine addiction.
“Adapting this approach for humans could be a promising way for blocking addiction,” Qingyao Kong, a postdoctoral researcher at the University of Chicago, wrote for The Conversation.
Kong was part of a team of researchers that demonstrated that skin grafting could be used in mice to reduce cocaine-seeking behaviors and make the mice less susceptible to overdose when given large amounts of cocaine. Their findings were published in the journal Nature Biomedical Engineering.
Humans naturally produce an enzyme called butyrylcholinesterase (BChE), which can break down cocaine into inactive, harmless components. BChE can be modified to metabolize cocaine even more rapidly than it naturally would, and has been identified as a possible treatment for cocaine addiction. However, it is tricky to deliver the active enzyme and keep it functioning.
To overcome this, Kong’s team tried using skin grafts to deliver the enzyme.
“So instead of giving the enzyme to the animals, we decided to engineer skin stem cells that carried the gene for the BChE enzyme,” Kong wrote. “This way the skin cells would be able to manufacture the enzyme themselves and supply the animal.”
To trial the idea on mice, the team first used gene editing to incorporate BChE into skin stem cells from a mouse.
“These engineered skin cells produced consistent and high levels of the hBChE protein, which they then secreted,” Kong wrote. Then, the cells were used to grow skin tissue in a lab, which was then grafted onto mice.
“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,” Kong wrote.
They were correct. Animals with the skin graft did not get the dopamine high when they dosed on cocaine, meaning they had no motivation to consume more. “Skin graft of the hBChE-cells efficiently blocks the cocaine-induced reward effect,” Kong explained.
In addition, it acted as an immunization against overdose. Half of the control mice exposed to large doses of cocaine died, but none of the mice with the graft did.
The team then tested whether human skin cells would also produce BChE after being modified, and found that they would.
“This suggests the concept of skin gene therapy may be effective for treating cocaine abuse and overdose in humans in the future,” Kong wrote. In addition, other enzymes that target alcohol and nicotine could potentially be used, allowing the skin graft technique to treat individuals with those addictions.
