I-Corps: Neural microphysiological systems for neuropharmaceutical testing

I-Corps：用于神经药物测试的神经微生理系统

• 批准号: 1439383
• 负责人: Michael Moore
• 金额: $ 5万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1439383&HistoricalAwards=false
• 关键词: Corps; Neural; microphysiological; systems; neuropharmaceutical

The technology described in this project represents a significant leap forward in the development of a neural 'organ-on-a-chip'. The ability to engineer a biomimetic 3D nerve model will allow for rapid screening of neurotoxicity, neuroprotection, as well as the tailoring of the microenvironment to mimic critical disease models. To this point, only 2D in vitro cell cultures and animal models have been available as pre-clinical tools for drug discovery. Unfortunately, neither of these options translates well to in vivo clinical applications, which is apparent looking at the current failure rates of drugs as well as skyrocketing R&D expenses. This advanced model will allow both academic and industrial scientists to further study underlying mechanisms and therapies related to neurodegenerative pathologies in a uniquely cost effective and timely manner. This technology should increase the molecular understanding of axonal degeneration, neurotoxic consequences and neuroprotective mechanisms. Successful commercialization of the proposed technology will result in a service-based product marketed towards pharmaceutical testing. The PI has demonstrated that microengineered peripheral neural tissues conduct electrically-evoked compound action potentials and filed a provisional patent related to the fabrication and application of the cell culture model. With this discovery as a foundation, the PI proposes to validate a prototype by demonstrating pathophysiological signatures in microengineered rat tissues. By contacting potential customers, the PI and his team will assess the readiness of the prototype and identify further benchmarks and design criteria. Two critical components will include refining the most effective outputs utilized for preclinical screenings and identifying maximally exploitable experimental paradigms.

该项目中描述的技术代表了神经“芯片器官”的开发方面的重大飞跃。设计仿生3D神经模型的能力将允许快速筛选神经毒性，神经保护性以及对微环境的量身定制以模拟关键疾病模型。至此，只有2D体外细胞培养物和动物模型可作为药物发现的临床前工具。不幸的是，这些选项都不能很好地转化为体内临床应用，这显然从药物的当前失败率以及飙升的研发费用。这种高级模型将使学术和工业科学家能够以独特的成本效益和及时的方式进一步研究与神经退行性病理相关的基本机制和疗法。该技术应增加对轴突变性，神经毒性后果和神经保护机制的分子理解。拟议技术的成功商业化将导致用于药品测试的基于服务的产品。 PI证明，微工程的周围神经组织会导致电诱发的复合作用电位，并提交了与细胞培养模型的制造和应用有关的临时专利。以这一发现为基础，PI提议通过在微工程大鼠组织中证明病理生理学特征来验证原型。通过与潜在客户联系，PI和他的团队将评估原型的准备就绪，并确定进一步的基准和设计标准。两个关键组件将包括精炼用于临床前筛选的最有效输出，并识别最大利用的实验范式。