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The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection – a novel disease-modifying osteoarthritis drug.

July 12, 2024

Arthritis Res Ther

Abstract BACKGROUND Despite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised […]

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From biochemical markers to molecular endotypes of osteoarthritis: a review on validated biomarkers.

February 1, 2024

Expert Rev Mol Diagn

Abstract INTRODUCTION Osteoarthritis (OA) affects over 500 million people worldwide. OA patients are symptomatically treated, and current therapies exhibit marginal efficacy and frequently carry safety-risks associated with chronic use. No disease-modifying therapies have been approved to date leaving surgical joint replacement as a last resort. To enable effective patient care and successful drug development there […]

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A novel biomarker of MMP-cleaved cartilage intermediate layer protein-1 is elevated in patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis.

December 7, 2023

Sci Rep

Abstract Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also […]

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Reflections from the OARSI 2022 clinical trials symposium: The pain of OA-Deconstruction of pain and patient-reported outcome measures for the benefit of patients and clinical trial design.

October 1, 2023

Osteoarthritis Cartilage

Abstract OBJECTIVE Osteoarthritis (OA) drug development is hampered by a number of challenges. One of the main challenges is the apparent discordance between pain and structure, which has had a significant impact on drug development programs and has led to hesitance among stakeholders. Since 2017, the Clinical Trials Symposium (CTS) has been hosted under the […]

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Biomarkers for osteoarthritis: Current status and future prospects.

June 1, 2023

Best Pract Res Clin Rheumatol

Abstract Osteoarthritis (OA) is the most common form of arthritis globally and a major cause of pain, physical disability, and loss of economic productivity, with currently no causal treatment available. This review article focuses on current research on OA biomarkers and the potential for using biomarkers in future clinical practice and clinical trials of investigational […]

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Serum biomarkers in prednisolone-treated hand osteoarthritis patients.

March 1, 2023

Rheumatology (Oxford)

Abstract OBJECTIVES To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. METHODS Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V […]

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R399E, A Mutated Form of Growth and Differentiation Factor 5, for Disease Modification of Osteoarthritis.

March 1, 2023

Arthritis Rheumatol

Abstract OBJECTIVE To preclinically characterize a mutant form of growth and differentiation factor 5, R399E, with reduced osteogenic properties as a potential disease-modifying osteoarthritis (OA) drug. METHODS Cartilage, synovium, and meniscus samples from patients with OA were used to evaluate anabolic and antiinflammatory properties of R399E. In the rabbit joint instability model, 65 rabbits underwent […]

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A Highly Sensitive Biomarker of Type II Collagen C-Terminal Pro-Peptide Associated with Cartilage Formation.

December 27, 2022

Int J Mol Sci

Abstract The type II collagen C-terminal pro-peptide is one of the most abundant polypeptides in cartilage. The purpose of this study was to develop a competitive chemiluminescence enzyme-linked immunosorbent assay, CALC2, targeting this pro-peptide as a marker of cartilage formation. Technical assay parameters were evaluated. CALC2 level was measured after in vitro cleavage of recombinant […]

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Clinical monitoring in osteoarthritis: Biomarkers.

September 1, 2022

Osteoarthritis Cartilage

Abstract OBJECTIVE The purpose of this overview of osteoarthritis (OA) biomarkers is to provide the non-specialist with a toolbox, based on experience acquired by biomarker researchers over many years, to understand biomarkers in general and their use in the OA field. METHODS We provide an update on this subject since the OARSI Primer on osteoarthritis […]

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Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: a pre-defined, exploratory biomarker analysis from the FORWARD study.

January 1, 2022

Osteoarthritis Cartilage

Abstract OBJECTIVE Osteoarthritis (OA) is characterized by the gradual loss of cartilage. Sprifermin, a recombinant FGF18, is being developed as a cartilage anabolic drug. PRO-C2 is a serum marker of type II collagen formation and low levels have been shown to be prognostic of radiographic progression. The aim of the study was to investigate whether […]

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