Higher Throughput Behavioral Screening of Cognitive Enhancers

描述（由申请人提供）：本申请是根据SBIR招标中NIMH研究课题J1，神经科学和基础行为科学和PA-04-086，高通量脑和行为工具的开发而提交的。我们的目标是通过CognoCube（tm）缓解认知功能障碍药物发现的瓶颈，这是一个自动化的高通量认知功能行为分析系统。CognoCube将包括创新的自动化测试、计算机视觉和机器学习算法，以捕获和集成影响认知功能的药物的行为影响。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有关。该系统将为新型认知增强剂的治疗潜力提供快速准确的指标。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学分析。在项目的第二阶段，CognoCube系统将扩大其能力，使其能够每年评估1000个化合物库。通过选择能够提供高可能性中枢神经系统活性的文库，我们预计每年能够在认知领域检测到多达12种具有中枢神经系统活性的新化合物。这些化合物将通过标准的认知测试进行进一步评估，并通过药理学手段和结合谱研究其作用机制。商业价值：仅在美国，估计就有超过3000万人可以从新的和改进的认知增强剂中受益。这一领域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。虽然标准化的客观测试电池已经开发出来用于评估人类的认知，但还没有这样的标准电池用于啮齿动物。我们的小鼠自动认知测试系统将提供比标准认知测试更高的可靠性，更大的统计能力和更高的吞吐量，并且凭借其在体内筛选文库的能力，将发现具有认知功效的新化合物。

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.