Higher Throughput Behavioral Screening of Cognitive

更高吞吐量的认知行为筛查

• 批准号: 7054033
• 负责人: Daniela Brunner
• 金额: $ 20万
• 依托单位: PSYCHOGENICS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-15 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054033
• 关键词: attention; behavior test; bioinformatics; biological models; biotechnology; cognition; computer system hardware; drug discovery /isolation; drug screening /evaluation; executive function; high throughput technology; laboratory mouse; model design /development; pharmacokinetics; psychopharmacologic agent; short term memory

DESCRIPTION (provided by applicant): This application is submitted in response to NIMH research topic J1, neuroscience and basic behavioral science in the SBIR solicitation and PA-04-086, development of high throughput tools for brain and behavior. We aim to alleviate the bottleneck in drug discovery for cognitive dysfunction with CognoCube(tm), an automated high-throughput system of behavioral analysis of cognitive function. CognoCube(tm) will comprise innovative automated testing, computer vision, and machine-learning algorithms to capture and integrate behavioral effects of drugs affecting cognitive function. CognoCube will capture many cognitive domains of high degree of homology between humans and rodents that are relevant in CNS disorders such as schizophrenia, dementia, attention-deficit disorder and ageing. This system will provide rapid and accurate indices of the therapeutic potential of novel cognitive enhancers. Phase I will be focused on proof of concept, namely, capture of behaviors relevant to targeted cognitive domains, sensitivity to pharmacological manipulation and robust bioinformatic analysis. The CognoCube(tm) system will expand its capacity during Phase II of the project to be able to assess a library of 1000 compounds per year. With libraries chosen to provide a high likelihood of CNS activity we expect to be able to detect up to a dozen new compounds per year with CNS activity in the area of cognition. Those compounds will be further assessed with standard tests of cognition and their mechanism of action will be studied through pharmacological means and binding profiling. Commercial value: The population that could benefit from new and improved cognitive enhancers is estimated at more than 30 million in the United States alone. Major challenges for drug discovery in this area include the lack of reliable and efficient in vivo testing systems. Although standardized objective test batteries have been developed for evaluation of human cognition, there is no such standard battery for rodents. Our automated cognitive testing system for mice will provide superior reliability, greater statistical power and higher throughput than standard cognitive tests and, with its power to screen libraries in vivo, will discover novel compounds with efficacy in cognition.

描述（由申请人提供）：此申请是针对NIMH研究主题J1，神经科学和基本行为科学的响应提交的，在SBIR招标和PA-04-086中，开发了用于大脑和行为的高通量工具。我们的目的是通过Cognocube（TM）（TM）的认知功能障碍来减轻瓶颈，Cognocube（TM）是一种自动化的高通量系统的认知功能行为分析。 Cognocube（TM）将包括创新的自动测试，计算机视觉和机器学习算法，以捕获和整合影响认知功能的药物的行为效应。 Cognocube将捕获人类与啮齿动物之间高度同源性的许多认知领域，这些认知与中枢神经系统疾病有关，例如精神分裂症，痴呆症，注意力缺陷障碍和衰老。该系统将提供新认知增强子的治疗潜力的快速准确指数。第一阶段将专注于概念证明，即捕获与靶向认知领域相关的行为，对药理学操纵的敏感性和强大的生物信息学分析。 Cognocube（TM）系统将在项目的第二阶段扩大其能力，以评估每年1000种化合物的库。随着库被选为提供CNS活动的很高可能性，我们希望能够发现每年多达十几种新化合物，并且在认知领域中有CNS活动。这些化合物将通过认知的标准测试进一步评估，其作用机理将通过药理学手段和结合分析来研究。商业价值：仅在美国，就可以从新的和改善的认知增强子中受益的人口就会超过3000万。在该领域发现药物发现的主要挑战包括缺乏可靠和有效的体内测试系统。尽管已经开发了标准化的客观测试电池来评估人类认知，但啮齿动物没有这样的标准电池。与标准认知测试相比，我们针对小鼠的自动认知测试系统将提供卓越的可靠性，更大的统计能力和更高的吞吐量，并且其在体内筛选库的能力将发现具有认知功效的新型化合物。