Research press release


Nature Biomedical Engineering

Gene therapy for treating cocaine addiction in mice



今回Ming Xu、Xiaoyang Wuたちは、概念実証研究で、BChEを産生するよう遺伝的に改変したマウス皮膚幹細胞を元のマウスの皮下に再埋植し、埋植した細胞がBChEを血流中に放出する拠点として長期にわたって働くことを示した。この処置は、条件付け場所嗜好性試験においてコカイン探索行動を減少させ、致死量のコカインを与えられたマウスの死を防いだ。

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.

doi: 10.1038/s41551-018-0293-z


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