Development of a Commercial Platform for Discovery and Validation of Key Microbial Metabolites in CNS Disorders

尽管有大量的持续资金和不断涌现的诊断和治疗方面的进步 在技术方面，中枢神经系统(CNS)疾病的负担仍然很大。物质使用的成本 仅混乱(SUD)一项就估计为1810亿美元(2002年)。负责识别风险的众多努力的结果 SUD的因素和致病因素表明，对依赖的易感性是一种受两者影响的复杂表型 遗传和环境因素。自闭症谱系障碍(ASD)似乎也在很大程度上受到这两种基因的影响 以及环境因素，更具体地说是肠道微生物群。 最近的研究表明，自闭症和自闭症共享共同的神经网络和分子信号。 小路。与ASD表型相关的几种基因产物(例如， 纹状体和基底节)影响神经元之间的突触传递，这也与成瘾有关 和奖励制度。此外，患有高功能自闭症的成年人对药物的敏感性更高。 依赖。我们假设，提高对ASD的当前认识状态，特别是关于 药物成瘾的共同属性，将启发新疗法的概念化和发展 纠正纹状体功能障碍常见因素的干预措施。 检验这一假设将需要一个经过验证的交钥匙平台，使客户能够将临床 来自受影响和未受影响的受试者的粪便样本，并收到由微生物组功能介导的代谢物列表 以及临床前(体内)数据包，破译中枢神经系统疾病的表型调节。有了这些资金 通过这个奖项，我们将设计、开发和商业化一种强大的中枢神经系统-微生物组-相互作用(CMI) 基于平台的服务，将使(I)阐明中枢神经系统疾病中新的微生物组介导的靶点，包括 代谢物、蛋白质和多肽，(Ii)在标准化动物模型中收集临床前数据，量化 微生物生物活性分子的影响，以及(Iii)在广泛的治疗领域中的应用，如SUD和 ASD.基于CMI平台的服务产品将允许医疗和制药公司客户(即我们的目标 市场)，以便从临床样本快速确定诊断和治疗目标并推断临床前疗效 估计没有对风险资本或复杂基础设施的投资。

Despite a wealth of continued funding and ever emerging advancements in diagnostic and therapeutic technologies, the burden of central nervous system (CNS) disorders remains substantial. The cost of Substance Use Disorder (SUD) alone is estimated at > $181 billion (2002). The findings of numerous efforts tasked with identifying risk factors and causative agents of SUD suggest that vulnerability to dependence is a complex phenotype influenced by both genetics and environmental factors. Autism Spectrum Disorder (ASD) also appears to be largely impacted by both genetic and environmental factors, more specifically the gut microbiome. Recent studies have demonstrated that autism and SUD share common neural networks and molecular signaling pathways. Several of the gene-products associated with the ASD phenotype (e.g., synaptic cell adhesion molecules in the striatum and basal ganglia) affect synaptic transmission between neurons, which has also been implicated in the addiction and reward system. In addition, adults afflicted with high functioning autism exhibit greater susceptibility to drug dependence. We hypothesize that advancing the current state of knowledge regarding ASD, with particular regard to the attributes shared with drug addiction, will inspire the conceptualization and development of novel therapeutic interventions to correct common elements of striatal dysfunction. Testing this hypothesis will require a validated turn-key platform enabling customers the ability to ship clinical fecal samples from affected and unaffected subjects and receive a list of metabolites mediated by microbiome functions and a pre-clinical (in vivo) data package deciphering the phenotypic modulation of the CNS disease. With the funding received through this award, we will design, develop, and commercialize a robust CNS-microbiome-interplay (CMI) platform-based service that will enable (i) elucidation of novel microbiome-mediated targets in CNS diseases, including metabolites, proteins and peptides, (ii) pre-clinical data collection in standardized animal models, quantifying the influence of microbial bioactive molecules, and (iii) application across a wide range of therapeutic areas, such as SUD and ASD. The CMI platform-based service offering will allow medical and pharmaceutical pharma customers (i.e., our target market) to rapidly define diagnostic and therapeutic targets from clinical samples and deduce pre-clinical efficacy estimates sans investment in venture capital or complex infrastructure.