Model System for In Vivo Testing of Bioscavengers

Current information indicates that bioterrorists have contemplated using organophosphate (OP) nerve agents against Americans. This situation points to a need for methods to detoxicate, decontaminate, and detect OP nerve agents. Human butyrylcholinesterase (hBchE) scavenges low doses of OP agents and protects people form the toxic effects, and is one of the main target enzymes being developed as a catalytic and/or stoichiometric chemical agent scavenger. We propose to develop an animal system that can offer systematic evaluation of the pharmacokinetic feature and immunogenicity of the protein reagent. In this system, a compatible animal protein will be tested in the same animal species Information derived from this homologous system will be used to predict the parallel human response. The system will also be used to evaluate different methodologies to produce stable form of recombinant BchE enzyme. The development of this homologous non-human system to evaluate BchE will provide guidelines for the manufacture and clinical use of recombinant hBchE.