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Cracking the Code to Cocaine Addiction A Stem cell story

CHRISTOPHER A. WHITE

"Modified skin stem cells may soon act as a therapeutic option to address drug abuse!"

Cocaine is an addictive drug commonly used in recreational settings. Longitudinal studies suggest 13% of American college students have tried cocaine, while 1.4% of Americans regularly use it! Until recently, no treatment existed for cocaine addiction, relapse, or overdose. However, recent findings demonstrate that stem cells may be the answer.

A single stem cell has the ability to give rise to many different cell types

Stem cells are simply cells that haven’t decided who they are, but when accepted into a new body have the potential to give rise to multiple cell types. Li and her colleagues recognized that the naturally occurring enzyme, Butyrylcholinesterase (BChE), can breakdown cocaine into less active and less rewarding molecules; leading them to ask, “can increased BChE concentrations combat cocaine addiction?”* The Answer: YES!!! However, BChE can’t simply be injected into the body as it will degrade rapidly. To circumvent this, the bioengineering technique CRISPR was used to generate easily transplantable skin stem cells that expressed BChE at above average rates.

Essentially, stem cells are the vehicle that carry the passenger, BChE, and this passenger gains access to the vehicle using specialized keys, a.k.a CRISPR.

Ultimately, skin stem cells were generated that led to increases in BChE in vitro (in test tubes). However, in order to be used clinically, this therapy had to work in the body first. Enter The MOUSE, our animal ‘participant’. When these cells were put into mice, they survived and grew normally, leading to BChE’s presence in the blood. As cocaine was administered it was degraded by BChE, resulting in decreased dopamine (brain molecule responsible for our interest in rewarding stimuli), making cocaine LESS rewarding! It was confirmed that cocaine was made less rewarding as mice spent reduced time in cocaine associated environments, indicating they were no longer seeking out cocaine. While the animals weren’t self administering the drug, the results imply that human addicts would have less motivation to use and seek out cocaine. Additionally, when lethal levels of cocaine was administered, no lethal overdoses were experienced because BChE significantly decreased blood cocaine concentrations. This has major implications for humans, as BChE reduces the likelihood of cocaine overdose if cocaine is taken.

Today, 1.5 million Americans abuse cocaine. Li and her colleagues have generated HUMAN stem cells that produce enhanced BChE expression in vitro. While still confined to a test tube, preliminary results indicate that this cell line is providing increased BChE levels, effectively decreasing cocaine concentrations; a potential first step towards protecting against cocaine addiction and overdose in humans.

Stem cells have already proven to be vital in a variety of medical applications. In fact, clinical trials are currently underway using stem cells to replace dying neurons in Parkinson’s patients after successfully doing so in mice! And while Li’s group hasn’t yet advanced to a clinical setting, they have created a sense of excitement and anticipation for future developments in the field.

Although stem cells garner the attention for Parkinson’s studies, their primary role in this study was to introduce BChE! Stem cells are the vehicle that deliver BChE without bodily rejection, raising the question, what other passengers can this vehicle transport? Beyond this, who should be the recipient of these transplants in the future? Should everyone be given preventative stem cell therapy just as they are given Chickenpox vaccinations in childhood? As research moves closer to human use, these questions will be at the forefront of future ethical conversations.

References

1. Kasperski SJ, S. (2011). College students’ use of cocaine: Results from longitudinal study. Addictive Behaviors, 36, 408-411. Retrieved February 17, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/21196083.

2. NIDA. (2018, July 13). Cocaine. Retrieved February 17, 2019, from https://www.drugabuse.gov/publications/drugfacts/cocaine.

3. Stem Cell Basics I. (2016, March). Retrieved February 17, 2019, from https://stemcells.nih.gov/info/basics/1.htm.

4. Li, Y., & Kong, Q. (2018). Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose. Nature Biomedical Engineering,3(2),105-113. doi:10.1038/s41551-018-0293-z

5. Cocaine at the Club [Digital Image]. (n.d.). Retrieved April 4, 2019, from http://www.sickchirpse.com/england-football-star-kicked-out-of-nightclub-aftersnorting-cocaine-at-the-club-christmas-party/ https

6. Why is Cell Differentiation Important [Digital Image]. (n.d.). Retrieved March 3, 2019, from https://biologywise.com/cell-differentiation

7. Confused Meme [Digital Image]. (n.d.) Retrieved March 3, 2019, from https://www.google.com/urlsa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjSk6P6o8ThAhVnUN8KHeYOA9kQjRx6BAgBEAU&url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3DrClNZLXSKA8&psig=AOvVaw0jKGTkZ5877QMLgOAcAjWj&ust=1554942795308464

8. The Drug Addiction of Mice and Men [Digital Image]. (n.d.) Retrieved March 4, 2019, from https://www.psychologytoday.com/us/blog/pop-psych/201509/the-drug addictions-mice-and-men

9. Hitchhiker Photo [Digital Image]. (n.d.). Retrieved April 5, 2019, from https://www.google.com/search?q=hitchhiker&source=lnms&tbm=isch&sa=X&v d=0ahUKEwioidaZv8ThAhWLUt8KHcGLAz0Q_AUIDygC&biw=1126&bih=599# mgrc=4iOYwfa9Ih51Mhttps://www.google.com/url?sa=i&source=images&cd=&c d=rja&uact=8&ved=2ahUKEwjSk6P6o8ThAhVnUN8KHeYOA9kQjRx6BAgBEA &url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3DrClNZLXSKA8& sig=AOvVaw0jKGTkZ5877QMLgOAcAjWj&ust=1554942795308464

10. Coke Mouse Taxidermy [Digital Image]. (n.d.) Retrieved April 29, 2019, from https://www.etsy.com/il-en/listing/600071104/made-to-order-coke-mouse-taxidermy?show_sold_out_detail=1

Created By
Christopher White
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