Researchers block cocaine craving and addiction with a special skin graft

Addiction to any drug – be it alcohol, tobacco, opioids or illicit drugs, like cocaine – is a chronic disease

Lines of cocaine. Christopher Slesarchik/Shutterstock.com

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.

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