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Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders

Award Number: R01AG067836
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders - Project Summary Age-related loss of memory remains a disease for which there are no effective treatments. Data suggests that an enzyme found in a specific region of the brain associated with memory, phosphodiesterase 11A (PDE11A), is increasingly expressed as humans age, and that levels of key signaling molecules in the brain that are substrates for this enzyme decrease in tandem, leading to the hypothesis that PDE11A is directly responsible for this effect. Our experiments with mice lacking PDE11A revealed that these animals behave and reproduce normally and do not suffer from the same age related loss of memory as their wild type littermates. This data collectively leads to the hypothesis that PDE11A may be a valuable target for study as a means to treat age-related loss of memory. There are no known potent and selective PDE11A inhibitors. A number of other PDE enzymes are under investigation or have been studied for various psychiatric and neurodegenerative diseases, indicating that this family can be targeted by small molecules. A novel screening method using yeast that express human PDE11A identified a number of good starting points. Some of these hits demonstrated excellent selectivity for PDE11A with the potential to be optimized to provide the first potent, selective PDE11A inhibitors with a profile that will allow us to investigate these compounds in mouse models of age-related behavior and memory.


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: 2024 ( Subtotal = $678,484 )
2024	2024	MONTCLAIR STATE UNIVERSITY	1 NORMAL AVE	MONTCLAIR	NJ	07043	ESSEX	USA	Aging Research	000	5	5/8/2024	NON-COMPETING CONTINUATION	$678,484
														Subtotal = $678,484

Issue Date FY: 2023 ( Subtotal = $726,045 )
2023	2023	MONTCLAIR STATE UNIVERSITY	1 NORMAL AVE	MONTCLAIR	NJ	07043	ESSEX	USA	Aging Research	000	4	4/20/2023	NON-COMPETING CONTINUATION	$726,045
														Subtotal = $726,045

Issue Date FY: 2022 ( Subtotal = $731,471 )
2022	2022	MONTCLAIR STATE UNIVERSITY	1 NORMAL AVE	MONTCLAIR	NJ	07043	ESSEX	USA	Aging Research	000	3	5/3/2022	NON-COMPETING CONTINUATION	$731,471
														Subtotal = $731,471

Issue Date FY: 2021 ( Subtotal = $737,807 )
2021	2021	MONTCLAIR STATE UNIVERSITY	1 NORMAL AVE	MONTCLAIR	NJ	07043	ESSEX	USA	Aging Research	000	2	5/4/2021	NON-COMPETING CONTINUATION	$737,807
														Subtotal = $737,807

Issue Date FY: 2020 ( Subtotal = $686,057 )
2020	2020	MONTCLAIR STATE UNIVERSITY	1 NORMAL AVE	MONTCLAIR	NJ	07043	ESSEX	USA	Aging Research	000	1	9/10/2020	NEW	$686,057
														Subtotal = $686,057

Grand Total All Awards = $3,559,864

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Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders

Award Number: R01AG067836

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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