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Metabolomic Profiling to Identify Candidate Biomarker Profiles and Molecular Endotypes for Osteoarthritis

Award Number: R01AR081489
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: 08/10/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Metabolomic Profiling to Identify Candidate Biomarker Profiles and Molecular Endotypes for Osteoarthritis - Project Summary Osteoarthritis (OA) affects more than 50 million people in the US, eventually leading to chronic pain and disability. Currently, no FDA-approved biomarkers for OA exist, limiting a clinician’s ability to detect early- stage disease. Early detection of OA is a rate-limiting step toward improved clinical care because recent studies show that early intervention can limit or reverse OA symptoms. However, early detection of OA is not currently possible. Metabolomic profiling is an innovative approach to characterize biological systems like synovial joints. While OA is classically described by degeneration of the articular cartilage, the pathophysiology of the disease involves cell stress, inflammatory activity, and abnormal tissue metabolism. Since the synovial fluid contains many of the molecules produced by the articular joint’s multiple cell types (eg chondrocytes, synoviocytes, and osteoblasts), metabolic profiling of the synovial fluid could provide a unique window into active disease processes in the OA-affected joint, and metabolomic profiles from synovial fluid could facilitate early detection of OA. While synovial fluid is “the scene of the crime” for OA, plasma is easier to obtain clinically. Because metabolites are smaller than 1000 Daltons, plasma metabolite profiles may also reflect OA pathophysiology, and the goal of this proposal is to advance global metabolite profiles as clinical biomarkers of OA grade. Our vision is to identify a panel of metabolite biomarkers that aid in the detection OA before the onset of symptoms. In Aim 1, metabolomic profiles of synovial fluid will be used with statistical learning to develop metabolite biomarkers that predict both radiographic (e.g. KL-score) and symptomatic (e.g. pain) OA. The largest available clinical cohort of human synovial fluid and plasma (n=1850, University of Oxford) will be used for metabolite biomarker development, with model training, testing, and validation performed on a random independent subsets. Because there is substantial heterogeneity in OA, molecular endotypes (i.e. molecular OA profiles) will be developed from these metabolomic profiles that may yield important information on OA pathophysiology. The cohort also contains paired plasma, and studies of Aim 2 will assess the correlations of each metabolite between synovial fluid and plasma. Because plasma is easier to obtain, these correlations will define which joint metabolites can be assessed in the circulatory compartment. The expected outcomes of this project are (1) a validated set of synovial fluid metabolite biomarkers that predict OA grade and pain levels (2) identification of metabolomic endotypes of OA, and (3) assessment of correlations between metabolite levels in the synovial fluid and the plasma. This will provide both clinicians and basic scientists with improved information for diagnosing and treating debilitating osteoarthritis.


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 = $418,609 )
2026	2026	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	8/7/2026	NON-COMPETING CONTINUATION	$418,609
														Subtotal = $418,609

Issue Date FY: 2025 ( Subtotal = $431,753 )
2025	2025	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	7/30/2025	NON-COMPETING CONTINUATION	$431,753
														Subtotal = $431,753

Issue Date FY: 2024 ( Subtotal = $463,869 )
2024	2024	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	7/26/2024	NON-COMPETING CONTINUATION	$463,869
														Subtotal = $463,869

Issue Date FY: 2023 ( Subtotal = $467,025 )
2023	2023	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/10/2023	NEW	$467,025
														Subtotal = $467,025

Grand Total All Awards = $1,781,256

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Metabolomic Profiling to Identify Candidate Biomarker Profiles and Molecular Endotypes for Osteoarthritis

Award Number: R01AR081489

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: 08/10/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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