Genetically modified skin stem cells protect mice from cocaine-seeking behaviour and cocaine overdose, suggests a paper published online this week in Nature Biomedical Engineering. Further research is needed to determine whether these findings can be translated to the clinic, but this approach may pave the way toward a new class of therapeutics for the long-term management of drug abuse.
Drug abuse, particularly of cocaine, is associated with compulsive drug-seeking and frequent relapsing despite long periods of abstention. Effective strategies to treat emergencies arising from cocaine overdose are needed, and behavioural and pharmacological treatment strategies developed to date have had limited success. Treatment with intramuscular injections of butyrylcholinesterase (BChE) - an enzyme optimized to degrade cocaine - has limited efficacy in animal models, in part owing to its short half-life.
In a proof-of-concept study, Ming Xu, Xiaoyang Wu and colleagues show that mouse skin stem cells genetically modified to produce BChE can be transplanted back under the skin of the same mouse to act as a depot for the long-term release of the enzyme into the bloodstream. This treatment reduced cocaine-seeking behaviour during conditioned place preference tests and prevented the death of mice exposed to lethal doses of cocaine.