Higher Throughput Behavioral Screening of Cognitive

描述(申请人提供)：本申请是针对NIMH研究课题J1，SBIR征集中的神经科学和基础行为科学，以及PA-04-086，高通量大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，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影响。CognoCube将捕捉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、痴呆症、注意力缺陷障碍和衰老等中枢神经系统疾病相关。该系统将为新型认知增强剂的治疗潜力提供快速和准确的指标。第一阶段将侧重于概念证明，即捕获与目标认知域相关的行为、对药物操纵的敏感性和稳健的生物信息学分析。CognoCube(Tm)系统将在项目第二阶段扩大其容量，以便能够评估每年1000个化合物的库。随着图书馆被选择来提供CNS活动的高可能性，我们预计每年能够检测到多达12个具有CNS在认知领域的活动的新化合物。这些化合物将通过标准的认知测试进行进一步评估，其作用机制将通过药理学手段和结合图谱进行研究。商业价值：仅在美国，可能受益于新的和改进的认知增强剂的人口估计就超过3000万。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。虽然已经开发了用于评估人类认知的标准化客观测试电池，但还没有用于啮齿动物的标准电池。我们的小鼠自动化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，并通过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.