Neucyte Inc

Nanoluciferase-based Ad/adrd Microphysiological Systems Platform for High-throughput Screening - Abstract Alzheimer Disease (AD) Is Characterized by B-amyloid (AB) Accumulation, Neurofibrillary Tangles (NFTS), Neuroinflammation, and Widespread Neuronal and Synaptic Loss. to Date, There Are No Therapies Available, Although Immunotherapies I.e., Lecanemab Hold Promise. Species Differences Underlie the Difficulties in Translating Therapeutics Uncovered in Animal Models for Human Brain-specific Diseases, E.g., Ad and Ad-related Dementia (adrd). Human Induced Pluripotent Stem Cell (HIPSC) Technological Advances Enable Better Human- Specific Disease Modeling, Particularly When Disease-related Genetic Mutations Are Absent in Murine or Rodent Models (e.g., Many Ad Gwas Genes), But Face Challenges Due to the Difficulty in Mimicking the in Vivo Context in Current in Vitro Models. Microphysiological Systems (MPS) With Defined Cellular Compositions Can Provide Scalable, Reproducible Brain Models That Better Recapitulate the in Vivo Environment, in Which Preclinical Drug Discovery Efforts Can Translate to a Higher Success Rate for Identified Targets and Compounds. This Project Proposes the Development of a Mini-brain Assembled Organoids (assembloids) Nanoluciferase-based Platform Using Ad Patient-derived APOE4 and Isogenic Gene-edited APOE3 Ipscs to Facilitate Effective and Reproducible Screening for Ad Therapeutics. Neucyte Employs Robust Differentiation Protocols to Generate Neurons, Astrocytes, and Microglia in Large Quantities Facilitating the Generation of Neuroimmune Assembloids (NIA) in Which the 3D Microenvironment Recapitulates Salient Ex Vivo Brain Phenotypes, E.g., Neurodegenerative and Cell-type Specific Phenotypes Due to a Genetic Mutation, Enabling Improved Translatable High-throughput Preclinical Drug Discovery. While Isogenic, This Platform Is Also Modular, I.e., Nluc Is Inserted in Different Contexts I.e., Reporter Lines in Different Cell Types Facilitating Mechanistic Cell Type-specific Assays Mimicking the Cellular Complexity of the Human Brain. the Ad/adrd MPS Nluc Platform Incorporates Bioluminescence-based Ad Neuropathological in Vitro Assays to Facilitate High-throughput Drug Screening. Successful Completion of Phase I Will Establish the Feasibility for Commercialization of an Ad/adrd Nluc Drug Screening Platform.