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Miniaturized AD/ADRD Microphysiological Systems Platform for High-throughput Screening

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AG084421-01
Agency Tracking Number: R41AG084421
Amount: $500,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIA
Solicitation Number: PAS22-197
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-01
Award End Date (Contract End Date): 2024-08-31
Small Business Information
Mountain View, CA 94043
United States
DUNS: 080117469
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (949) 824-8700
Business Contact
Phone: (714) 620-9601
Research Institution
SAN FRANCISCO, CA 94143-2510
United States

 Nonprofit College or University

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) microfluidics 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., the impact of a mutation in microglia can be studied to model
effects on neurons facilitating mechanistic studies mimicking the cellular complexity of the human brain. The
AD/ADRD MPS microfluidic platform incorporates acoustic technology and enables economical examination of
AD pathology in vitro facilitated by miniaturization, reducing costs associated with cell numbers, reagents, and
drug library quantities to facilitate high-throughput drug screening. Successful completion of Phase I will establish
the feasibility for commercialization of an AD/ADRD drug screening platform.

* Information listed above is at the time of submission. *

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