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Exploring the convergence of small vessel diseases of the brain using novel gene-edited rat models (MODEL-CSVD)

Award Number: RF1NS143914
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: 09/08/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Exploring the convergence of small vessel diseases of the brain using novel gene-edited rat models (MODEL-CSVD) - Cerebral small vessel diseases (CSVD) are a major cause of vascular cognitive impairment and dementia (VCID) in the elderly, account for a significant number of ischemic and hemorrhagic strokes and are present in Alzheimer’s disease and related disorders (ADRD). With an increasing aged population in the US the consequences of CSVD will only intensify. Despite the significance of this problem, there are currently no effective therapies for CSVDs presenting an unmet clinical need. The overall hypothesis of our proposal is gene-edited rat models of CSVD will provide superior preclinical platforms of these conditions to interrogate pathogenic mechanisms. We plan to thoroughly vet a novel suite of recently generated rat models of CSVD, resulting from distinct etiologies, that lead to similar deleterious cerebral events and VCID, conditions that strongly impact the elderly and patients with Alzheimer’s disease and related disorders (ADRD). CSVDs broadly fall into two classes: 1) amyloidal CVSD including sporadic and familial forms of cerebral amyloid angiopathy (CAA), a condition that is prominent in ADRD and 2) non-amyloidal CSVD involving common conditions such as hypertension, diabetes, and a number of monogenic hereditary forms including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). Each of these distinct CVSDs present with prominent cerebral vessel wall alterations, ischemic and hemorrhagic strokes, progressive white matter damage and VCID. To investigate the molecular pathogenesis of CSVD/VCID, identify new biomarkers, and to more effectively interrogate new therapeutic approaches appropriate preclinical animal models are needed that faithfully recapitulate human disease. The proposed work will deliver a set of currently lacking, much needed preclinical models required as the platforms for the subsequent timely studies to address disease mechanisms, biomarker discovery, and therapeutic testing for CSVD and VCID, all key objectives outlined by NINDS.


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: 2026 ( Subtotal = $1,766,928 )
2026	2026	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE RD RM 103	KINGSTON	RI	02881	WASHINGTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/8/2026	NEW	$1,766,928
														Subtotal = $1,766,928

Grand Total All Awards = $1,766,928

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Exploring the convergence of small vessel diseases of the brain using novel gene-edited rat models (MODEL-CSVD)

Award Number: RF1NS143914

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: 09/08/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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