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

这是Neurxstem Inc.的SBIR提案，被NCET 2评选为“最佳大学”的公司 Startups 2016是对NIH HEAL倡议的回应。Neurxstem的目标是开发和 优化专有的诱导多能干细胞衍生的人神经类器官平台 （NNOP）开发1）物质（SUD）和阿片类药物（OUD）使用的早期诊断NNOP 疾病的易感性和2）确定早期治疗目标，为未来的筛选有效 SUD/OUD疾病相关药物发现、疗效和安全性筛选。的当前状态 用于这些目标的现有技术的范围从人原代和永生化细胞系到啮齿动物 模型因为这些模型不能很好地替代复杂的网络结构， 人类大脑，该平台有望填补转化神经科学的一个关键空白 目的是了解和治疗人类大脑疾病。Neurxstem开发了专有的 方法，使几乎完整的人类神经类器官，并已表明，一个上级 NNOP与其他具有大脑所有主要部分的“类器官”相比-视网膜，皮层， 中脑，后脑和脊髓-在一个单一的，网络化的和可扩展的NNOP，也 表达所有主要细胞类型，包括与SUD密切相关的小胶质细胞， 对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是一家由Rene Anand博士创立的小型企业， 发明人提出进一步开发这种临床证实的模型系统，以测试其 商业转化神经科学的可靠性、再现性、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法确定早期治疗靶点：1）基因的数学建模 表达数据对成瘾药物的响应，以推断SUD/OUD的早期生物标志物。相 目的：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 与制药的发展。第二个目标是使用多个SUD扩展和验证平台 患者iPSC系，以证明：a）可靠性，B）重现性和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，Neuxstem的商业化计划 包括1）潜在客户对产品验证的市场反馈; 2）初始市场进入 与测试版客户/业务合作伙伴合作;以及3）持续知识产权开发和 起诉从根本上说，Neurxsem的NNOP的进一步开发和验证 应该提供更低成本、更精确和准确的系统，用于个性化、预测性、 SUD/OUD的诊断医学和对策的发展。

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.