Research project
Investigating the anti-inflammatory potential of the PRG4 protein in preventing and alleviating rheumatoid arthritis
Can the protein PRG4 help to prevent or alleviate the symptoms of rheumatoid arthritis?
- Contact
- Menno Hoekstra
- Funding
- Kiem grant (Leiden University)
Rheumatoid arthritis is a chronic inflammatory disorder that leads to the progressive destruction of bone and cartilage in the joints. Recent studies suggest that the protein proteoglycan 4 (PRG4), which plays a key role in joint lubrication and has anti-inflammatory properties, could be a promising new avenue for preventing or alleviating the symptoms of rheumatoid arthritis. This research aims to explore the potential anti-inflammatory and protective benefits of PRG4 in treating this debilitating condition.
Research goal
The goal of this project is to explore the anti-inflammatory potential of the protein PRG4 in treating rheumatoid arthritis. By combining expertise in PRG4’s biological functions and rheumatoid arthritis, the research aims to develop new therapeutic strategies and clinical applications to prevent or alleviate the symptoms of this debilitating condition.
Interdisciplinary approach
The collaboration between the Leiden Academic Centre for Drug Research (LACDR) and the Leiden University Medical Center (LUMC) brings together a powerful combination of knowledge in protein function and clinical rheumatology.
This project combines expertise from two distinct fields: Assistent Professor Menno Hoekstra’s preclinical research on the physiological and pathological functions of PRG4 and Professor of Experimental rheumatology Rene Toes' world-leading work on rheumatoid arthritis. By bridging these areas of expertise, the project aims to uncover a potential new therapeutic target for rheumatoid arthritis and expand its investigation into clinical applications.
Faculty of Science: Menno Hoekstra
Leiden University Medical Centre: Sanne Kampstra (Postdoc) en Rene Toes (Head of Department), Department of Rheumatology
Project description: The anti-inflammatory function of the lubricant proteoglycan 4: shifting the therapeutic focus from atherosclerotic cardiovascular disease to rheumatoid arthritis
Recent studies in mice genetically lacking the protein PRG4 have shown that this naturally produced lubricant plays a protective role in preventing atherosclerosis (narrowing of the arteries due to plaque buildup). A follow-up study has confirmed that giving mice a recombinant (laboratory-made) human version of PRG4 (rhPRG4) reduces atherosclerosis susceptibility. The protective effect of rhPRG4 is likely due to its ability to reduce inflammation in the body, specifically by lowering the levels of an inflammation inducing protein called tumour necrosis factor-alpha (TNF-α).
Importantly, TNF-α is also a major driver of rheumatoid arthritis, a painful condition that causes damage to the joints over time. In this pilot study, we will combine the expertise of Dr. Menno Hoekstra, who specialises in understanding how PRG4 works, and Prof. Dr. Rene Toes, who is a leading expert in rheumatoid arthritis. Together, they will investigate whether rhPRG4 could help treat rheumatoid arthritis. The researchers will test rhPRG4 in a mouse model with a form of arthritis that is induced by administering an antibody cocktail, a method used to mimic the human disease. If the study shows promising results, it could lead to new ways of using PRG4 in rheumatoid arthritis treatment or as a marker to detect the disease earlier.