Preclinical Testing of Antibody Therapy for METH Abuse

冰毒滥用抗体疗法的临床前测试

• 批准号: 6776888
• 负责人: Samuel Michael Owens
• 金额: $ 116.67万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6776888
• 关键词: drug abuse; drug abuse therapy; methamphetamine; monoclonal antibody

The goal of this transdisciplinary program project is to facilitate the rapid development of new medications for the treatment of medical problems associated with (+) -methamphetamine [(+)METH]abuse. This will be accomplished through a well-integrated and highly focused research program, designed to manufacture and test monoclonal antibody-based therapy for METH abuse and/or addiction. Project 1 (the core unit) will provide strong leadership, vital supply and support services that include large scale monoclonal antibody production, immunochemical and LC/MS/MS analysis for pharmacokinetic studies, and integrated data analysis of the research findings. Project 2 will use rat and monkey models of human drug dependencies to test the effectiveness of the medications in reducing the addictive properties of (+)METH. These studies will include testing of the antibodies in self-administration and drug discrimination paradigms. Project 3 will determine the efficacy, duration of action and safety of the medications in disease models of acute and chronic drug use. Thee animal models will span a range of human use patterns from infrequent usages to dangerous "binge" usage of (+)METH. Measures of locomotor activity and hemodynamic effects, along with changes in the general health status of the animals, will be used to determine the ability of the medications to reduce effects even in the presence of binge use of (+)METH. Project will involve developing the technology for maximizing large scale, low cost production of the antibodies through the development of advanced agrimedicine manufacturing technology. DNA that codes for anti-(+)METH antibody will be introduced into plants enabling the expression and accumulation of pharmaceutical grade monoclonal antibodies on a very large scale and at an acceptable cost. The results of the studies in this multifaceted program project will serve as the initial preclinical testing of these important new medications for the treatment of the devastating consequences of the (+)METH dependence and abuse.

这个跨学科计划项目的目标是促进新药物的快速开发，用于治疗与（+）-甲基苯丙胺[（+）METH]滥用相关的医疗问题。这将通过一个高度整合和高度集中的研究计划来实现，该计划旨在制造和测试基于单克隆抗体的METH滥用和/或成瘾治疗。项目1（核心单位）将提供强有力的领导、重要的供应和支持服务，包括大规模单克隆抗体生产、用于药代动力学研究的免疫化学和LC/MS/MS分析以及研究结果的综合数据分析。项目2将使用人类药物依赖性的大鼠和猴子模型来测试药物在减少（+）METH成瘾性方面的有效性。这些研究将包括在自我给药和药物辨别范例中检测抗体。项目3将确定药物在急性和慢性药物使用疾病模型中的疗效、作用持续时间和安全性。这些动物模型将涵盖一系列人类使用模式，从不经常使用到危险的“狂欢”使用（+）METH。。将使用运动活动和血流动力学效应的测量沿着动物一般健康状况的变化来确定药物降低效应的能力，即使在存在（+）METH的狂欢使用的情况下。项目将涉及通过开发先进的农业医药制造技术，开发最大限度地大规模、低成本生产抗体的技术。编码抗（+）METH抗体的DNA将被引入植物中，使得能够以非常大的规模和可接受的成本表达和积累药用级单克隆抗体。在这个多方面的计划项目的研究结果将作为这些重要的新药物的治疗（+）METH依赖和滥用的破坏性后果的初步临床前测试。