Nerve agent testing

神经毒剂测试

基本信息

批准号：
7689887
负责人：
Douglas Mark Cerasoli
金额：
$ 12.46万
依托单位：
U.S. ARMY MEDICAL RESEARCH INST CHEM DEF
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7689887
关键词：
Active Sites Animal Model Animal Testing Animals Attention Basic Science Binding Blood Blood Circulation Brain Brain Injuries Cavia Chemical Weapons Chemicals Computer Simulation Core Facility Data Development Dose Drug Kinetics Effectiveness Ensure Enzymes Gases Goals Hydrolysis In Vitro Mass Spectrum Analysis Measures Mediating Medical Mission Modeling Modification Mutation Neuraxis Numbers Pharmaceutical Preparations Poison Poisoning Positioning Attribute Process Proteins Relative (related person)Research Research Institute Research Project Grants Resources Safety Saline Scientist Specialist Specificity Test Result Testing Toxic effect Training United States Food and Drug Administration assay development base bioscavenger design experience gallium alloy GF in vivo interdisciplinary approach mutant nerve agent next generation novel novel strategies pre-clinical programs prophylactic research facility research study

项目摘要

The goal of the Organophosphorus Nerve Agent Testing (ONAT) Core, a component of the Center for Catalytic Bioscavenger Medical Defense Research, is to test the mutant enzymes produced by other Research Projects in the Center for in vitro and in vivo efficacy against organophosphorus (OP) nerve agents. The results from this testing will contribute directly to the development of a pretreatment that offers complete protection from poisoning by OPs. The core is located at the US Army Medical Research Institute of Chemical Defense, a singular national resource with a highly trained staff of scientists supported by safety, surety, and environmental specialists who ensure regulatory compliance of experiments involving highly toxic surety agents such as OP nerve agents. The mission of the USAMRICD is the development of medical countermeasures against chemical weapons, which is precisely aligned with the mission of the CounterACT initiative. The ONAT core is uniquely positioned to assess the function of anti-OP bioscavengers against bona fide nerve agents; the use of these highly toxic agents is restricted to a very limited number of research facilities worldwide. The tests to be conducted by the core will include characterization of the OP nerve agent reactivity, specificity, and stereoselectivity of candidate bioscavenger enzymes using a combination of colorimetric, calorimetric, and gas chromatographic/mass spectroscopy approaches. The capacity of different enzymes to persist in the circulation of a model test animal, and the protection from OP toxicity afforded by these enzymes will also be evaluated. The multidisciplinary approach of the ONAT core to assay development and efficacy testing will support the development of a 'next generation' bioscavenger molecule with the potential to bind and destroy OP nerve agents in the blood, before they distribute to the brain, central nervous system, and other toxic targets. In this regard it is important that the USAMRICD, and in particular the PI of the Center as well as the PI for this core component, have experience in both basic science and in early product development, meaning attention will constantly remain focused on not only the scientific issues, but also on the requirements to develop a novel, protein based drug product that will protect against the otherwise toxic effects of OP nerve agent exposure. The goal of the CounterACT program is to create new ways to protect ourselves from toxic chemicals like OP nerve agents. The goal of this core proposal is to test how well these new approaches defend against highly toxic nerve agents. Without the testing that will be conducted by this core, which is unique in its access to OP nerve agents, there will be no way to measure the effectiveness of these new approaches.

有机磷神经毒剂测试 (ONAT) 核心的目标是该中心的组成部分催化生物清除剂医学防御研究，是测试其他生物产生的突变酶中心的研究项目针对有机磷（OP）神经的体外和体内功效代理。该测试的结果将直接有助于预处理的开发，该预处理可提供完全防止 OP 中毒。核心位于美国陆军医学研究所化学防御，一个独特的国家资源，拥有训练有素的科学家人员，由安全、保证和环境专家，确保涉及的实验符合法规剧毒保证剂，例如 OP 神经毒剂。 USAMRICD 的使命是发展针对化学武器的医疗对策，这与联合国的使命完全一致 CounterACT 倡议。 ONAT 核心具有独特的定位，可以评估抗 OP 的功能针对真正的神经毒剂的生物清除剂；这些剧毒剂的使用仅限于非常有限的范围全球范围内的研究设施数量有限。核心进行的测试将包括候选生物清除剂的 OP 神经毒剂反应性、特异性和立体选择性的表征结合比色、量热和气相色谱/质谱分析酶接近。不同酶在模型试验动物循环中持续存在的能力，以及还将评估这些酶对 OP 毒性的保护作用。多学科方法 ONAT 核心的分析开发和功效测试将支持“下一个具有结合和破坏血液中OP神经毒剂潜力的“一代”生物清除剂分子，在它们分布到大脑、中枢神经系统和其他有毒目标之前。在这方面它是重要的是 USAMRICD，特别是该中心的 PI 以及该核心的 PI 组件，具有基础科学和早期产品开发经验，这意味着注意力将不仅要不断关注科学问题，还要关注开发小说的要求，基于蛋白质的药物产品将防止 OP 神经毒剂暴露的其他毒性作用。 CounterACT 计划的目标是创造新的方法来保护我们自己免受有毒化学品的侵害，例如 OP神经毒剂。该核心提案的目标是测试这些新方法如何有效防御剧毒神经毒剂。没有由该核心进行的测试，该核心的独特之处在于获得OP神经毒剂后，将无法衡量这些新方法的有效性。