A recent study led by Dr. Ming Xu and Dr. Xiaoyang Wu at the University of Chicago suggests that the use of gene-editing techniques, such as CRISPR, combined with skin grafting could help combat serious drug addiction and protect individuals from overdose.
The study, which was performed using mice, involved harvesting skin stem cells and genetically modifying them to express an enhanced variant of an enzyme responsible for breaking down cocaine, followed by re-implantation of these modified stem cells back into the mouse via a skin graft. Mice who received the treatment were found to be protected against cocaine-seeking behavior and also survived lethal doses of cocaine.
This research expands upon the work of Dr. Chang-Guo Zhan at the University of Kentucky, who designed an enhanced variant of the human enzyme butyrylcholinesterase (BChE), which metabolises cocaine into harmless components.
Through delivering this enzyme into a host via a skin graft, the enhanced cocaine-metabolising enzyme is able to stay present in the body at high levels and increase the rate of cocaine breakdown. This increased breakdown of cocaine into harmless components not only prevented addictive responses but also protected against lethal overdose.
The authors went on to show that engineered human skin cells were also capable of expressing high amounts of the modified BChE , indicating these results could be reproduced in humans.
In the US, between 1.5%–2% of the population is predicted to use cocaine and in 2017 almost 15,000 individuals died of overdose. In recent years, overdose deaths due to natural and synthetic opioids have spiked drastically and account for over 60% of all drug-related overdose deaths in the US.
If tissue grafts designed to deliver high levels of protective enzymes could be fully adapted for human use, it is possible that not only could cocaine addiction and related deaths be curbed, but so could the negative effects of powerful opioids, such as fentanyl.