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CNS Stem Cells for neurodegenerative disease research

Award Number: R21AG044720
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2014
PERIOD OF PERFORMANCE END DATE: 05/31/2017

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CNS Stem Cells for neurodegenerative disease research - DESCRIPTION (provided by applicant): Neurodegenerative protein misfolding diseases, the most common of which is Alzheimer's disease (AD), exact devastating personal and economic tolls on society. CNS stem cell (CNS-SC) transplantation has been touted, justifiably, as a promising approach for treatment of Alzheimer's disease (AD) and other degenerative brain diseases either by replacing lost cells or as a vehicle for delivery of therapeutic agents. CNS-SC transplantation also may offer new approaches for dissecting disease processes and mechanisms. The broad aim of this pilot project is to assess and refine neurosphere transplantation as a tool to dissect pathogenic mechanisms and spread of tau pathology. Two paradigms will be explored: 1) transplantation of CNS-SC containing neurospheres from mice that do not develop disease into disease models, and 2) transplantation of neurospheres from disease models into mice that do not develop disease. The substrate for these pilot studies is the well-characterized rTg(tauP301L)4510 model for the tauopathy frontotemporal dementia (FTD). AD is characterized by extracellular Ass amyloid plaques and intracellular neurofibrillarly tangles (NFTs) composed of aggregated tau protein. Of the two, NFTs are more tightly associated with cognitive decline, neuron loss, and dementia than are plaques, arguing for the relevance of the FTD model for AD as well as other tauopathies. Evidence suggests that soluble extracellular forms of tau, rather than intracellular neurofibrillary tangles (NFTs), may be the triggers of neuronal dysfunction and cell death. Experiments will compare transplants of neurospheres from eGFP-expressing tau null and mouse tau-expressing mice into newborn rTg(tauP301) and rTg(tauwt) mice that express comparable levels of human mutant or wild type tau, and track cell survival, differentiation into neurons, and synapse formation by the progeny of the transplanted cells. In addition to addressing the question of whether endogenous tau expression is required for deleterious effects of extracellular tau aggregates, replacement of lost host neurons will be assessed. The project will address the questions of whether neurons from rTg(tauP301L) neurospheres develop tauopathy and whether spread of tauopathy is influenced by mismatching of tau primary structures in the transplant and the host. Refined methods and tools will be developed to facilitate application of stem cell transplantation to understanding disease mechanisms; these should prove valuable beyond this specific project.


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: 2017 ( Subtotal = $0 )
2017	2015	MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC., THE	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Aging Research	000	2	9/28/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $208,550 )
2015	2015	MCLAUGHLIN RESRCH INSTITUTE FR BIOMEDICAL SCIENCES, INC	1520 23RD STREET, SOUTH	GREAT FALLS	MT	59405	CASCADE	USA	Aging Research	000	2	6/17/2015	NON-COMPETING CONTINUATION	$208,550
														Subtotal = $208,550

Issue Date FY: 2014 ( Subtotal = $258,000 )
2014	2014	MCLAUGHLIN RESRCH INSTITUTE FR BIOMEDICAL SCIENCES, INC	1520 23RD STREET, SOUTH	GREAT FALLS	MT	59405	CASCADE	USA	Aging Research	000	1	8/12/2014	NEW	$258,000
														Subtotal = $258,000

Grand Total All Awards = $466,550

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CNS Stem Cells for neurodegenerative disease research

Award Number: R21AG044720

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2014

PERIOD OF PERFORMANCE END DATE: 05/31/2017

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