Neurxtem Neural Organoid Human Platform Development for Substance and Opioid Use Disorders

这是一份由NCET2评选为最佳大学的神经干细胞公司的SBIR建议书 初创企业2016“是对NIH Hear倡议的回应。神经干细胞的目标是开发和 一种专有诱导多能干细胞来源的人神经器官样细胞平台的优化 (NNOP)开发1)物质(SUD)和阿片类药物(OUD)使用的早期诊断NNOP 障碍易感性和2)确定早期治疗靶点，以便将来进行有效筛查 SUD/OUD疾病相关药物的发现、疗效和安全性筛选。的当前状态。 实现这一目标的ART技术范围从人类原代和永生化细胞系到啮齿动物 模特们。因为这些模型不能很好地替代复杂的网络结构 人脑，拟议的平台有望填补翻译神经科学的一个关键空白 了解和治疗人类大脑疾病的目标。神经干细胞已经开发出了专有的 制作几乎完整的人类神经有机体的方法学，并已显示出优越的 NNOP与其他拥有大脑所有主要部分-视网膜、皮质、 中脑、后脑和脊髓-在单一、联网且可扩展的NNOP中 表达所有主要的细胞类型，包括与SUD密切相关的小胶质细胞 对一种成瘾药物的反应改变了与多种药物相关的多种生物标志物 虐待。Neurxstem是由Rene Anand博士创立的一家小企业，技术之一 发明者建议进一步开发这一经临床证实的模型系统以测试其 商业翻译神经科学的可靠性、重复性、稳健性和实用性 申请SUD/OUD，并在FDA批准后启动市场准入。第一阶段目标： 第一阶段的目标是通过以下方式识别早期治疗靶点：1)对基因进行数学建模 表达数据对成瘾药物的反应以推断SUD/OUD的早期生物标记物。阶段 II目标：一个目标是通过数学建模确定所有可能的早期治疗靶点 用于未来SUD/OUD对策的多个数据点和药物暴露样本 与医药共同发展。第二个目标是使用多个SUD扩展和验证平台 患者IPSC展示：a)可靠性、b)重复性和c)稳健性指标 需要证明早期诊断和药物发现的全部效用、有效性和安全性 测试SUD/OUD的商业目标。此外，Neuxstrom的商业化计划 包括1)潜在客户对产品验证的市场反馈；2)初步进入市场 与测试版客户/业务合作伙伴合作；以及3)持续的知识产权开发和 起诉。从根本上说，神经干细胞NNOP的进一步发展和验证 应该提供一个成本更低、更精确和准确的个性化、预测性系统 SUD/OUD的诊断医学及对策发展。

This is a SBIR proposal from Neurxstem Inc., a company selected by NCET2 as a “Best University Startups 2016” is in response to the NIH HEAL initiative. Neurxstem’s goals are to develop and optimize a proprietary induced pluripotent stem cell derived human Neural Organoid Platform (NNOP) to develop 1) an early diagnostic NNOP for substance (SUD) and opioid (OUD) use disorder susceptibility and 2) to identify early therapeutic targets for future screens for effective SUD/OUD disease-related drug discovery, efficacy and safety screening. The current state of the art technology for such goals ranges from human primary and immortalized cell lines to rodent models. Because these models are poor surrogates for the complex network structure of the human brain, the proposed platform is expected to fill a crucial gap in translational neuroscience goals to understand and treat human brain disorders. Neurxstem has developed the proprietary methodology to make nearly complete human neural organoids and has shown that a superior NNOP compared to other ‘organoids’ that has all the major parts of the brain – retina, cortex, midbrain, hindbrain, and spinal cord - in a single, networked and scalable NNOP that also expresses all the major cell types including the microglia critically involved in SUD and exhibits responses to a drug of addiction that alters a multitude of biomarkers linked to multiple drugs of abuse. Neurxstem, a small business founded by Dr. Rene Anand, one of the technology inventors, proposes to further develop this clinically corroborated model system to test its reliability, reproducibility, robustness and utility for commercial translational neuroscience applications for SUD/OUD and initiate market entry after FDA approval. Phase I Aims: The Phase I goals are to identify early therapeutic targets by: 1) mathematical modeling of gene expression data responses to drugs of addiction to deduce early biomarkers for SUD/OUD. Phase II Aims: One goal is identify all possible early therapeutic targets by mathematical modeling from multiple data points and drug exposure samples for future SUD/OUD countermeasure development with Pharma. A second goal is to scale and validate the platform with multiple SUD patient iPSC lines to demonstrate: a) reliability, b) reproducibility and c) robustness metrics needed to demonstrate the full utility for early diagnostic and drug discovery, efficacy and safety testing commercial goals for SUD/OUD. Additionally, Neuxstem’s commercialization plan includes 1) market feedback from prospective clients for product validation; 2) initial market entry with beta customers/ business partners; and 3) continuing intellectual property development and prosecution. Fundamentally, the further development and validation of Neurxstem’s NNOP should provide a lower cost, more precise and accurate system for personalized, predictive diagnostic medicine and development of countermeasure for SUD/OUD.