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Cellular and Molecular Mechanisms of IL-17A in the Pathogenesis of Psoriatic Arthritis

Award Number: R01AR084848
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Cellular and Molecular Mechanisms of IL-17A in the Pathogenesis of Psoriatic Arthritis - Project Summary/Abstract Psoriatic arthritis is a chronic and progressive inflammatory arthritis closely linked with psoriasis. Blockade of the IL-17 signaling pathway shows impressive efficacy and excellent safety for treatment of psoriasis but less so for PsA. Tissue penetrance limits the bioavailability of monoclonal antibodies to the joint and fibrocartilaginous enthesis and IL-17A signaling is diversified by local immune cells in tissues rendering IL-17A inhibition less effective. A higher dosage poses the risks of serious infections and certain types of cancer as all IL-17 inhibitors are immunosuppressive therefore to improve clinical outcomes in PsA more selective targeting is required. Herein, we have developed a novel animal model of IL-17A gene transfer where mice develop joint and skin inflammation associated with enthesitis, fingernail psoriasis and onycholysis hallmarks of PsA pathology. We will interrogate our murine model to define the early cellular and molecular pathways that dictate IL-17A-induced pathologies using state-of-the-art transgenic mice and molecular tools. Our work will uncover the pathogenic mechanisms of IL-17A and uncover novel molecular targets that can be exploited for therapeutic intervention and directly benefit PsA patients worldwide.


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 = $664,933 )
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/14/2025	NEW	$664,933
														Subtotal = $664,933

Grand Total All Awards = $664,933

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Cellular and Molecular Mechanisms of IL-17A in the Pathogenesis of Psoriatic Arthritis

Award Number: R01AR084848

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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