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A new class of wet AMD therapeutics

Award Number: R01EY034247
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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A new class of wet AMD therapeutics - ABSTRACT Advanced neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), in which neovessels originating from the choroid invade the macula. CNV causes permanent central blindness if left untreated and is the most sight-threatening pathology of AMD. The present application will investigate the efficacy and regulatory mechanisms for a new class of CNV therapeutics. We have identified in our preliminary data that ketone bodies suppress CNV and hypothesize that this effect is regulated by macrophage and/or microglia reprogramming, which results in protective inflammation and/or suppression of pathological inflammation. We will refute or validate this hypothesis in three Specific Aims. In Aim 1, we will determine the therapeutic effects of ketone metabolites and their potential synergistic effect with anti-VEGF therapies, the current standard of care for CNV. We will also determine whether the anti-angiogenic effects of ketone metabolites are regulated by direct effects on endothelial cells or ketone-induced immune cell phenotypic changes using co-culture models. In Aim 2, we will identify whether ketone bodies suppress CNV via microglia, macrophages recruited from the circulation, or both. In Aim 3, we will determine the role of the ketone body receptor, G Protein-coupled receptor 109a (Gpr109a) in phenotypic reprogramming of specific immune cell subpopulations.


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 = $0 )
2025	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Vision Research	001	2	12/5/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$335,711
2025	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Vision Research	002	2	12/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	1	12/5/2024	NEW	-$335,711
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $377,500 )
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Vision Research	001	2	9/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$377,500
2024	2023	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	1	9/6/2024	NEW	$0
														Subtotal = $377,500

Issue Date FY: 2023 ( Subtotal = $391,250 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	1011 E 51ST ST	KANSAS CITY	MO	64110	JACKSON	USA	Vision Research	000	1	8/30/2023	NEW	$391,250
														Subtotal = $391,250

Grand Total All Awards = $768,750

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A new class of wet AMD therapeutics

Award Number: R01EY034247

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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