Catalytic Antibodies as Therapy for Drug Addiction

催化抗体治疗毒瘾

• 批准号: 6892951
• 负责人: Kim Janda
• 金额: $ 42.23万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892951
• 关键词: abzyme; amphetamines; biotechnology; catalyst; chordate locomotion; cocaine; drug abuse chemotherapy; drug addiction; haptens; immunopharmacology; laboratory mouse; laboratory rat; monoclonal antibody; nicotine; pharmacokinetics; recombinant DNA

DESCRIPTION (provided by applicant): The problem of drug addiction continues to plague society. In particular, cocaine, amphetamines, and nicotine represent the major substances of abuse leading to dependence and significant behavior modification. A number of pharmacotherapies and psychosocial programs have been implemented over the years to aid in cessation, detoxification and relapse prevention with limited success. Cocaine abuse remains prevalent, people continue to smoke, a variety of amphetamines litter the recreational drug market, and the abuse of heroin is on the rise especially among adolescents, all with alarming statistics. In this regard, alternative therapies are crucial, either as stand-alone treatments or to complement those already in existence, if progress is to be made in treating substance dependence. This proposal provides the foundation of an immunopharmacological therapy for drug addiction based on catalytic monoclonal antibodies (mAbs) that degrade drugs of abuse. The specific aims encompass 1) anti-cocaine catalytic mAb investigations in a rat locomotor model for testing efficacy, pharmacokinetics, and improvements in catalytic activity using cutting-edge recombinant DNA and structure-based strategies. Some mAbs nave been prepared and are ready for study. As improved catalysts become available from antibody engineering, they will be characterized and then tested in rats. 2) Synthesis of haptens to elicit catalytic mAbs specific for the degradation of amphetamines and nicotine. The novel hapten designs are derived using a "bait and switch" approach developed in our laboratory. Preliminary studies of mAbs against MDMA ("ecstasy") are in progress. Rationales are presented for the requirements of catalytic mAbs with regard to drug dependence in humans and their eventual realization as clinical therapeutics. Although the complete elimination of drug addiction may be an ideal, catalytic mAbs along with other pharmacological agents and counseling programs to alleviate addiction problems would prove beneficial for society.

描述（由申请人提供）：吸毒问题继续困扰社会。特别是可卡因，苯丙胺和尼古丁代表了导致依赖性和重大行为修改的滥用的主要物质。多年来，已经实施了许多药物治疗和社会心理计划，以帮助停止，排毒和预防复发，并取得有限的成功。可卡因滥用仍然很普遍，人们继续吸烟，各种苯丙胺乱扔娱乐性药物市场，而海洛因的滥用也在增加，尤其是在青少年中，所有这些都具有令人震惊的统计数据。在这方面，如果要在治疗物质依赖性方面取得进展，替代疗法是至关重要的，要么是独立治疗，要么是已经存在的疗法。该建议为基于催化单克隆抗体（MAB）的药物成瘾的免疫药物疗法提供了基础，从而降解了滥用药物的药物。具体目的包括1）使用尖端的重组DNA和基于结构的策略，用于测试功效，药代动力学和催化活性改善的大鼠运动模型中的抗可卡因催化MAB研究。一些mab的中殿已经准备好并准备好学习。随着抗体工程的改进催化剂的改善，它们将被表征并在大鼠中进行测试。 2）合成触发的合成，以引起针对苯丙胺和尼古丁降解的特异性催化mAb。新颖的Hapten设计是使用我们实验室开发的“诱饵和开关”方法得出的。对MDMA（“摇头丸”）的mAB的初步研究正在进行中。对于人类的药物依赖性及其最终作为临床疗法的催化mAb的要求提出了理由。尽管完全消除吸毒成瘾可能是理想的，但催化器单击以及其他药理学剂以及减轻成瘾问题的咨询计划将证明对社会有益。