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Testing Lifespan/Healthspan Pharmacological Interventions in Humanized C. elegans Knock-In Models of Dementia

Award Number: R43AG061978
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2020

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Testing Lifespan/Healthspan Pharmacological Interventions in Humanized C. elegans Knock-In Models of Dementia - By 2050, over 15 million people in the USA will be diagnosed with Alzheimer'srelated dementia at an annual treatment cost near $200 billion. To contain the escalation in healthcare costs, new treatments are needed to relieve the underlying genetic causes and risk factors leading to dementia onset. In simple animal models, drugs have been found that lead to lifespan extension. Yet the underlying genetic mechanisms as drug targets for Alzheimer'srelated dementia remain elusive. In this SBIR proposal, humanized animal models are created to model genetic disorders of the Frontotemporal Dementia (FTD) component of Alzheimer'sDiseaseRelated Dementias (ADRD). Four FTD genes are targeted for humanization (MAPT, GRN, C9orf72, and TARDBP) in the C. elegans animal model. The procedure for humanization resulting genespecific replacement with human cDNA. Using a CRISPRbased Geneswap technique, a sequenceoptimized human gene is inserted as a replacement of an orthologous gene in the genome of the animal model. Each humanized animal creates a platform for installing and profiling the functional consequence of pathogenic variants. The variants causing deviant phenotypes are screened for the capacity of longevityassociated molecules to restore wildtype phenotype. If FTD model creation and compound screening reveal a restorative capacity, the assay system can then be used for discovery of novel therapeutic molecules. Leads discovered are commercialized by internal or externallylicensed drug development into therapeutics for treating FTD disease.


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: 2021 ( Subtotal = $0 )
2021	2018	NEMAMETRIX, INC	1505 WESTEC DR	EUGENE	OR	97402	LANE	USA	Aging Research	000	1	3/12/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $350,000 )
2018	2018	NEMAMETRIX, INC	44 W 7TH AVE	EUGENE	OR	97401	LANE	USA	Aging Research	000	1	9/18/2018	NEW	$350,000
														Subtotal = $350,000

Grand Total All Awards = $350,000

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Testing Lifespan/Healthspan Pharmacological Interventions in Humanized C. elegans Knock-In Models of Dementia

Award Number: R43AG061978

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2020

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