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Amyloid Beta Oligomer Induction of Alzheimer's Disease in Nonhuman Primates

Award Number: R43OD023025
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/2018
PERIOD OF PERFORMANCE END DATE: 03/07/2019

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Amyloid Beta Oligomer Induction of Alzheimer's Disease in Nonhuman Primates - PROJECT SUMMARY Patients with Alzheimer's disease (AD) suffer a progressive loss of memory and cognitive ability, and eventual loss of basic bodily functions and death. Currently 11% of Americans over 65 have AD and its incidence and toll on the healthcare system continues to rise with significant societal impact. There are no treatments for AD to prevent its inexorable course, and a principal obstacle to developing new therapies for AD has been the inadequacy of available preclinical modeling, which almost exclusively involves rodents. As nonhuman primates (NHPs) share greater homology to humans than rodents in all respects, including genomics and physiology, cognitive processing, neuronal network complexity, white/gray matter ratios, dynamics of drug/target interactions, and the triggers of age-associated pathophysiology, the long-term goal of this project is to develop a new NHP model of AD that can be standardized and deployed in rigorous, reproducible studies to overcome critical current deficiencies in translating preclinical studies into novel clinical diagnostic strategies and therapies. The objective of this application is to expand and advance recent preliminary work on a new NHP model of AD involving intrathecal administration of amyloid β-oligomers (AβOs). The hypothesis is that AβOs will trigger a cascade of accelerated pathology that mimics the changes occurring in the brains of AD patients. This hypothesis is based on a growing consensus in the AD research field, backed by strong data, that AβOs are likely the toxic species that provoke deposition of the characteristic tangles and plaques in the brain together with loss of synapses and neurons and associated cognitive decline. The hypothesis will be tested in statistically meaningful designs by pursing the following two specific aims: 1) Determine the appropriate dose of AβO and intervals of dosing; and 2) Identify the persistence of induced biochemical and structural deficits and AD pathology following termination of AβO infusion. These studies will utilize in-life (MRI) and post-mortem measurements (immunohistochemistry, biochemistry) to establish the impact of AβOs administration in the brain of the St. Kitts green monkey, a species that has been well characterized for its propensity to develop naturally occurring features of AD pathology. The approach is innovative because it represents a substantial shift from current AD research paradigms and tests a novel theoretical concept. The research is significant because it is expected to overcome critical deficiencies in current animal AD models by validating an accelerated, inducible NHP model of sporadic AD and permit effective translation of basic studies into novel clinical diagnostic strategies and therapies. Success with this model development program would provide a valuable resource to academic, biotechnology, pharmaceutical and diagnostic laboratories in need of a reliable preclinical model of AD for basic research, and diagnostic and therapeutic development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	VIRSCIO, INC.	4 SCIENCE PARK	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Infrastructure Programs	001	1	12/21/2019	SUPPLEMENT FOR EXPANSION	$0
2020	2017	VIRSCIO, INC.	4 SCIENCE PARK	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	National Center for Advancing Translational Sciences	000	1	12/4/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $49,018 )
2018	2018	RXGEN INC	100 DEEPWOOD DR	HAMDEN	CT	06517	SOUTH CENTRAL CT	USA	Research Infrastructure Programs	000	1	9/19/2018	SUPPLEMENT FOR EXPANSION	$49,018
														Subtotal = $49,018

Issue Date FY: 2017 ( Subtotal = $208,412 )
2017	2017	RXGEN INC	100 DEEPWOOD DR	HAMDEN	CT	06517	SOUTH CENTRAL CT	USA	National Center for Advancing Translational Sciences	000	1	9/6/2017	NEW	$208,412
														Subtotal = $208,412

Grand Total All Awards = $257,430

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Amyloid Beta Oligomer Induction of Alzheimer's Disease in Nonhuman Primates

Award Number: R43OD023025

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/20/2018

PERIOD OF PERFORMANCE END DATE: 03/07/2019

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