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Tau mislocalization assay to screen AD therapeutics using compartmentalized chips

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AG072985-01A1
Agency Tracking Number: R43AG072985
Amount: $535,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: R
Solicitation Number: PAS19-316
Solicitation Year: 2019
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-02-01
Award End Date (Contract End Date): 2024-01-31
Small Business Information
76 TW Alexander Dr., PO Box 14205
Research Triangle Park, NC 27709
United States
DUNS: 026927928
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (951) 553-6400
Business Contact
Phone: (919) 240-7909
Research Institution

Neurofibrillary tangles, a hallmark of Alzheimer's disease (AD), are formed following tau dissociation from
microtubules and mislocalization to the somatodendritic compartment of affected neurons. Pathological tau is
then released from affected neurons and spreads trans-synaptically eventually leading to cell death.
Preventing the initial mislocalization of intracellular tau within the somatodendritic compartment presents an
early therapeutic target and may lead to strategies that limit the progression of AD. Xona Microfluidic, Inc.
(“Xona”) proposes to develop a reliable, reproducible, and scalable screening assay to identify and validate
therapeutic targets that prevent early mislocalization of intracellular tau. The goal of this project is to establish
the feasibility of providing preclinical screening services using this assay for AD and AD-related diseases.
Preliminary data suggests that tau mislocalization can be modeled in Xona's proprietary compartmentalized
microfluidic chips by restricting exposure of Aβ-induced neuroinflammatory media to the axonal compartment.
The resulting tau mislocalization correlates with an increase in synaptic vesicle release, which is consistent
with AD pathophysiology. Xona proposes to develop this screen on the basis of this preliminary data and using
human induced pluripotent stem cell differentiated neurons cultured in 3D, which more closely mimic human
disease phenotypes than murine models. Aim 1 will determine the extent to which 3D cultures improve
synapse maturation over 2D cultures using these neurons within our compartmentalized chips. Aim 2 will
develop a tau mislocalization assay using Aβ-induced neuroinflammatory media. Further, we will evaluate the
reliability and suitability of this assay for drug screening using an established metric of screening potential.
Once feasibility is shown, Xona will focus on forming partnerships with potential customers and scaling up the
number of compounds that can be screened.

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

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