Treating cocaine addiction with viruses
Treating cocaine addiction with viruses
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DOI：
10.1073/pnas.0403795101
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发表时间：
2004-07-13
影响因子：
11.1
通讯作者：
Janda, KD
中科院分区：
文献类型：
--
作者：
Carrera, MRA;Kaufmann, GF;Janda, KD
可卡因成瘾仍然是美国和其他国家的主要健康和社会问题。事实证明，目前用于治疗可卡因滥用的药物不够充分，治疗选择很少。另一种方法是使用蛋白质为基础的治疗方法，可以消除可卡因的负荷，从而减弱其影响。这种方法特别有吸引力，因为治疗剂本身不发挥药效学作用，因此副作用的可能性很小。然而，这些药物的有效性受到其不能直接作用于CNS的限制。当鼻内施用时，噬菌体具有穿透CNS的能力。在这里，提出了一种方法工程丝状噬菌体展示可卡因结合蛋白在其表面上，螯合可卡因在大脑中。这些抗体展示的构建体进行了检查，通过使用运动活动啮齿动物模型，以评估噬菌体展示的蛋白质阻断可卡因的精神作用的能力。所呈现的结果表明了持续努力寻找可卡因成瘾有效治疗方法的策略，并建议将这种基于蛋白质的治疗方法应用于其他药物滥用综合征。
Cocaine addiction continues to be a major health and social problem in the United States and other countries. Currently used pharmacological agents for treating cocaine abuse have proved inadequate, leaving few treatment options. An alternative is to use protein-based therapeutics that can eliminate the load of cocaine, thereby attenuating its effects. This approach is especially attractive because the therapeutic agents exert no pharmacodynamic action of their own and therefore have little potential for side effects. The effectiveness of these agents, however, is limited by their inability to act directly within the CNS. Bacteriophage have the capacity to penetrate the CNS when administered intranasally. Here, a method is presented for engineering filamentous bacteriophage to display cocaine-binding proteins on its surface that sequester cocaine in the brain. These antibody-displaying constructs were examined by using a locomotor activity rodent model to assess the ability of the phage-displayed proteins to block the psychoactive effects of cocaine. Results presented demonstrate a strategy in the continuing efforts to find effective treatments for cocaine addiction and suggest the application of this protein-based treatment for other drug abuse syndromes.