Enhancing Treatment Strategies for Osteoarthritis: Targeting Microenvironmental Proinflammatory Sialic Acid Signaling

Research Project, 2022 – 2026

Therapeutic options for patients suffering from osteoarthritis (OA) remains a major clinical challenge, 25% of individuals above 56 are affected. In OA, cartilage repair malfunctions and creates a proinflammatory microenvironment.
I have shown that such microenvironmental changes can be used for specific therapeutic strategies. Here, I propose several goals towards precision medicine in OA based on the clinical findings that the glycoprotein modification sialic acid (SA) is enhanced in OA joints. The complex structures of glycoproteins pose a great challenge, and multidisciplinary approaches and novel tools are crucial to unveil their pathogenic role. The first goal uses glycoproteomics and immunological assays to identify a potential new biomarker in OA synovial fluid. The second goal determines SA-driven pathogenic mechanisms by clarifying how SA cell-expression affects cellular crosstalk and cartilage composition using immunological tools and physicochemical approaches. Third, I provide two novel treatment strategies using unique inflammation-specific SA blocking nanoparticles, one that targets ongoing synovial inflammation and one that utilizes the cartilage to inhibit early SA-signals in chronic OA. Using both patient material and animal models, these studies increase our understanding of how SA changes contribute to inflammation, synovial hypertrophy and cartilage damage in immune-mediated OA and evaluates a potential disease-modifying therapeutic approach.