Preclinical Testing of Antibody Therapy for METH Abuse

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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.