Administration and management

行政和管理

基本信息

批准号：
7920103
负责人：
DAVID E LENZ
金额：
$ 11.71万
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/7920103
关键词：
Academic Medical Centers Acetylcholinesterase Address Adoption Advanced Development Agreement Algae Antidotes Area Arizona Back Baltimore Biochemical Biological Blood Blood Circulation Butyrylcholinesterase Capital Chemical Agents Chemical Warfare Chemical Warfare Agents Chemical Weapons Chemicals Chemistry China Cholinesterase Inhibitors Clinical Trials Collection Conflict (Psychology)Costs and Benefits Coupled Databases Drug Metabolic Detoxication Ensure Enzymes Ethiopia Evaluation Exposure to General Population Genes Genetic Engineering Germany Goals Human Human Activities Human Resources Hydrolase Hydrolysis In Vitro Insecticides Institutes Institution International Iran Iraq Israel Japan Kinetics Laboratories Lead Mammalian Cell Maryland Medical Medical Research Military Personnel Modeling Modification Molecular Molecular Biology Molecular Evolution Molecular and Cellular Biology Mutate Nature Office of Administrative Management Ohio Organism Paraoxon Pathway interactions Pesticides Pharmaceutical Preparations Plants Plasma Poison Poisoning Population Process Production Proteins Recombinants Research Research Infrastructure Research Institute Research Project Grants Resources Sarin Series Site Source Stream Structural Protein Synapses System Techniques Technology Testing Therapeutic Time Toxic effect Translations United States National Institutes of Health Universities Vertebrates Vulnerable Populations Work World War II X-Ray Crystallography animal resource aryldialkylphosphatase base bioscavenger combinatorial chemistry computational chemistry cost design drug development drug discovery drug production efficacy evaluation emergency service responder feeding improved in vivo mutant nerve agent novel programs prophylactic protein complex protein expression research clinical testing response skills success tool toxicant transmission process weapons

项目摘要

Two proteins, human plasma BuChE, and a recombinant human BuChE are both in advanced development as potential prophylacitcs for protecting against chemical warfare agents. These proteins react rapidly and stoiciometrically to effectively scavenge the poisons in the blood stream but they require relatively large amounts of protein to provide protection. The challenge of identifying a protein based drug that would require less material while providing improved protection with the advantage of enhanced user acceptance cannot be ignored. Recent efforts the laboratories alinged with the Center have identified several human enzymes, paraoxonase (PON) and a mutant of butyrylcholinesterase that can catalyze the hydrolysis of all nerve agents. As such these are excellent candidate for prophylactic administration to provide protection for first responders to a terrorist attack or military forces in a civilian peacekeeping setting subject to an asymmetric threat. If it were administered intravenously it could also serve as a rapid-onset therapeutic antidote to a segment of the civilian popuation exposed to nerve agents. Preliminary studies have shown that these objectives are both feasible and obtainable. The cost/benefit ratio of such a drug is such that it is an excellent candidate for success and has the potential to be the first in a series of a novel class of drugs. The center will coordinate the overall effort directed toward the enhancement of the the native catalytic activity of these human enzymes to create a viable candidate for transition to advancement to clinical trials within a five year period. This will address a critical gap in the national goal of protecting the civilian population against a terrorist-initiated chemical weapons attack. Current medical protection against chemical nerve agent exposure by terrorists is limited to post exposure treatment. We will identify and develop for clinical testing a human protein capable of providing rapid and long lasting prophylactic protection against exposure to chemical warfare nerve agents. Such a drug will address the critical national goal of providing improved protection to the general population against a terrorist-initiated chemical weapons attack.

两种蛋白质，人血浆Buche和一个重组人Buche都在高级发育中作为预防化学战剂的潜在预防。这些蛋白质反应迅速，用sto菌，有效地清除血液中的毒药，但需要相对较大提供保护的蛋白质量。识别基于蛋白质的药物的挑战在提供增强用户接受的优势的同时，需要更少的材料，同时提供改进的保护不能忽略。最新的努力，该中心的实验室已经确定了几个人酶，二氧化二氧蛋白酶（PON）和丁酰胆碱酯酶的突变体，可以催化所有人的水解神经毒剂。因此，这些是预防施法的绝佳候选者在平民维持和平环境中，对恐怖袭击或军事力量的第一响应者不对称威胁。如果静脉注射给药，也可以用作快速发作的治疗对暴露于神经毒剂的平民群体的解毒剂。初步研究表明这些目标既可行又可获得。这种药物的成本/收益率是如此是成功的出色候选人，并有可能成为一系列新型药物中的第一个。该中心将协调针对增强天然催化的整体努力这些人类酶的活性，以创建一个可行的候选者，以过渡到临床试验在五年内。这将解决保护平民的国家目标的一个危险差距人口反对恐怖分子发起的化学武器攻击。当前对化学神经毒剂暴露恐怖分子暴露的医疗保护仅限于接触治疗。我们将确定并开发用于临床测试的人蛋白，能够提供快速和持久的预防性保护防止暴露于化学战神经剂。这样的药物会解决了为普通民众提供改进保护的关键国家目标恐怖分子发起的化学武器攻击。