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Dopamine and Sigma Receptor Mixed Modulators for the Treatment of Alzheimer's Disease

Award Number: R16NS140308
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/04/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Dopamine and Sigma Receptor Mixed Modulators for the Treatment of Alzheimer's Disease - An estimated 1-in-8 individuals over the age of 65 has Alzheimer’s disease (AD), with a prevalence of 1-in-3 for those over age 85. There are approximately 5.8 million people in the USA with AD, with a global projection of over 150 million by 2050. Given the limited state of therapeutic options, a viable therapeutic approach that is not redundant with current medications would be of great benefit to AD patients and caregivers. Sigma receptors (σ1 and σ2) and dopamine receptors (D2 and D3) have been respectively attracting attention as brain targets for Alzheimer’s disease (AD) treatment. We have developed a small molecule (AM73) with affinity for σ1/σ2 and D2/D3 receptors. This mixed modulator approach is novel and presents a viable means to treat cognitive decline and associated symptomology. This proof-of-concept study evaluates the mixed modulator AM73 in a mouse model of cognitive decline and AD. Aims of the study focus on determining the effect of chronic treatment of AM73 across a dose-response respective to behavior and locomotor responses in male and female mice. Key brain regions associated with AD pathology and targeted receptors will be evaluated for changes in mRNA and protein expression respective to pathological indicators and treatment markers. The goal and aims of this study address priorities of National Institute on Aging.


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: 2025 ( Subtotal = $144,500 )
2025	2025	BOARD OF TRUSTEES OF SOUTHERN ILLINOIS UNIVERSITY	#5 HAIRPIN DRIVE	EDWARDSVILLE	IL	62026	MADISON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/1/2025	NON-COMPETING CONTINUATION	$144,500
														Subtotal = $144,500

Issue Date FY: 2024 ( Subtotal = $141,647 )
2024	2024	BOARD OF TRUSTEES OF SOUTHERN ILLINOIS UNIVERSITY	#5 HAIRPIN DRIVE	EDWARDSVILLE	IL	62026	MADISON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/3/2024	NEW	$141,647
														Subtotal = $141,647

Grand Total All Awards = $286,147

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Dopamine and Sigma Receptor Mixed Modulators for the Treatment of Alzheimer's Disease

Award Number: R16NS140308

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/04/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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