Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine.
Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine.
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DOI：
10.1016/j.neuropharm.2020.108251
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发表时间：
2020-10-01
影响因子：
4.7
通讯作者：
Zhan CG
中科院分区：
文献类型：
--
作者：
Zhang T;Wei H;Deng J;Zheng F;Zhan CG
开发一种真正有效的治疗物质使用障碍(SUD)的方法是一个巨大的挑战，特别是对于没有FDA批准的治疗方法的可卡因和其他药物，因为真正有效的治疗方法必须在整个治疗期间有效地阻止药物的生理和强化作用，以实现FDA要求的长期戒断。一种生物学方法，如单抗、疫苗或治疗性酶，是否能真正有效地治疗SUD一直是广泛争论的主题。主要的争论问题是，一种生物酶，特别是一种外源性酶，是否能有效地阻止药物的增强作用。在这份报告中，我们证明了适度剂量的最近重新设计的长效可卡因水解酶CocH3-FC(M6)可以在足够长的一段时间内有效地阻断可卡因的心理刺激、歧视性刺激和强化效应。例如，剂量为3 mg/kg的CocH3-FC(M6)在24/25天内完全阻断大鼠的辨别性刺激和增强效应，并在至少29天内继续显著减弱/减少可卡因的效应。所有的动物数据一致表明，长效可卡因水解酶是治疗可卡因使用障碍的酶疗法的一个真正有希望的候选者。
It is a grand challenge to develop a truly effective treatment of substance use disorder (SUD), particularly for cocaine and other drugs without an FDA-approved treatment available, because a truly effective therapy must effectively block the drug’s physiological and reinforcing effects during the entire period of treatment in order to achieve the long-time abstinence required by the FDA. Whether a biologic, such as monoclonal antibody, vaccine, or therapeutic enzyme, can be truly effective for SUD treatment or not has been the subject of extensive debate. The main debate question is whether a biologic, particularly an exogenous enzyme, can effectively block the drug’s reinforcing effect. In this report, we demonstrate that a modest dose of a recently redesigned long-acting cocaine hydrolase, CocH3-Fc(M6), can be used to effectively block the psychostimulant, discriminative stimulus, and reinforcing effects of cocaine for a sufficiently long period of time. For example, a dose of 3 mg/kg CocH3-Fc(M6) completely blocked the discriminative stimulus and reinforcing effects for 24/25 days and continued to significantly attenuate/decrease the cocaine effects for at least 29 days in rats. All the animal data consistently suggest that the long-acting cocaine hydrolase is a truly promising candidate of enzyme therapy for treatment of cocaine use disorder.
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影响因子：
14.8
作者：
Solinas, Marcello;Panlilio, Leigh V.;Goldberg, Steven R.
通讯作者：
Goldberg, Steven R.
影响因子：
5.1
作者：
Chen, Xiabin;Deng, Jing;Zheng, Fang
通讯作者：
Zheng, Fang
DOI：
10.1073/pnas.0507332102
发表时间：
2005-11-15
影响因子：
11.1
作者：
Pan, YM;Gao, DQ;Zhan, CG
通讯作者：
Zhan, CG
慢性可卡因自我给药的禁欲改变了恒河猴中的纹状体多巴胺系统。
DOI：
10.1038/npp.2008.135
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Schindler CW;Justinova Z;Lafleur D;Woods D;Roschke V;Hallak H;Sklair-Tavron L;Redhi GH;Yasar S;Bergman J;Goldberg SR
通讯作者：
Goldberg SR