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

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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.