Preclinical drug discovery research for Alzheimer's Disease (AD) is hampered by the lack of sufficient preclinicalmodels. Although several drugs have shown promise in animal models to some extent, many human clinicaltrials of therapies for AD have failed. Therefore in vitro models using human-derived cell lines or patient-derivedgenetically-manipulated human induced pluripotent stem cells (hiPSC) that overexpress the different isoforms ofβ-amyloid have shown interest. These hiPSCs with the acquisition of full cellular functionality, microenvironmentmechanostructural cues and mimicking vascular defects observed in patients with AD are in development.Further, blood-brain-barrier (BBB) integrity that prevents neurotoxins from entering the brain and bidirectionalmolecular communications between the central nervous system and the enteric nervous system, are critical forAD therapeutic strategy in the laboratory models. These models with 3D perfused engineered micro-sized organsystems can help costly and risky drug testing with quantitative and mechanistic data. However, high throughputportable passive system that can connect multiple organs and provide quantitative pharmacokinetics data, is stillto be realized. Therefore, Biopico Systems Inc teams with UC Irvine to propose a Humanized Organ PlateParadigm (HOPP) for high throughput Alzheimer's disease therapeutics that can accurately and reproduciblymimic the AD phenotype in vivo and be amenable to high-content screening and assay applications. With thepreliminary results from the patent-pending organ platform and measurement instrumentation, Biopico will utilizeexisting drugs that have failed in clinical trials and given positive indications to perform proof-of-concept of ourplatform. The Phase I research aims are to: (i) Develop functional blood-brain-barrier in vitro pharmacologicalHOPP system in high throughput format, (ii) Integrate multi-organs for morphological, functional, geneexpression & metabolic markers metrics and (iii) Validate HOPP system using pharmacokinetic modeling and invitro to in vivo extrapolation. The successful completion of these aims will provide a strong foundation fordeveloping a commercial organ system in Phase II to customers developing therapeutic agents for AD. Biopico'svision is to commercialize the largescale application of the screening assay to accelerate the process of findinga disease-modifying therapy. Narrative We will develop the multi-organ high throughput PK/PD screening in humanized in vitro drug testing for AD. The development of this high throughput body-on-a-chip platform with patient-specific stem cells and immune cells is a powerful new approach to advance AD therapeutics. 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