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）：本申请是为了响应 NIMH 研究主题 J1（SBIR 征集中的神经科学和基础行为科学）以及 PA-04-086（大脑和行为高通量工具的开发）而提交的。我们的目标是利用 CognoCube(tm) 缓解认知功能障碍药物发现的瓶颈，CognoCube(tm) 是一种认知功能行为分析的自动化高通量系统。 CognoCube(tm) 将包括创新的自动化测试、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 将捕获人类和啮齿动物之间高度同源的许多认知领域，这些领域与精神分裂症、痴呆、注意力缺陷障碍和衰老等中枢神经系统疾病相关。该系统将提供新型认知增强剂治疗潜力的快速、准确的指标。第一阶段将侧重于概念验证，即捕获与目标认知领域相关的行为、对药理学操作的敏感性和强大的生物信息分析。 CognoCube(tm) 系统将在项目第二阶段扩大其容量，以便能够每年评估包含 1000 种化合物的库。通过选择提供高可能性 CNS 活性的库，我们预计每年能够检测到多达十几种在认知领域具有 CNS 活性的新化合物。这些化合物将通过标准认知测试进一步评估，并通过药理学手段和结合分析研究其作用机制。商业价值：据估计，仅在美国就有超过 3000 万人口可以从新的和改进的认知增强剂中受益。该领域药物发现的主要挑战包括缺乏可靠且高效的体内测试系统。尽管已经开发出用于评估人类认知的标准化客观测试电池，但对于啮齿动物还没有这样的标准电池。我们的小鼠自动化认知测试系统将比标准认知测试提供卓越的可靠性、更强的统计能力和更高的吞吐量，并且凭借其体内筛选库的能力，将发现具有认知功效的新型化合物。