Identifying new drugs to prevent and treat osteoarthritis

Understanding early processes in osteoarthritis: paving the way for novel drugs (HypOA)

Osteoarthritis is a disease of the locomotor system characterised by degeneration of cartilage and underlying bone. Recent publications have indicated changes in the properties of cartilage cells occur (chondrocytes) before the tissue is damaged. The consortium hypothesises that intervention in the pathway of these early changes in chondrocytes will prevent progression of osteoarthritis into a chronic disabling disease. With this partnership Erasmus MC and Galapagos will generate more knowledge on the changes that chondrocytes undergo during osteoarthritis and develop laboratory models to help develop new treatments.

Osteoarthritis is a painful and disabling disease and there currently is no cure. It has been identified as a serious disease determining morbidity and mortality in elderly. The number of Dutch osteoarthritis patients will almost double to 2.3 million patients in 2040. Without effective intervention in this disease the central mission of LSH to add at least five years in good health to the lives of all Dutch citizens by 2040, is unachievable. To develop an effective pharmacological treatment, we need to intervene in key pathways early in the disease. To obtain more insight in molecular processes that initiate these changes and in the progression of the phenotypical changes the consortium will develop models to study whether and how blood vessels and inflammation (both occurring in early stages of osteoarthritis) stimulate changes in chondrocyte behaviour. Finally, the consortium will channel these results into creating a lab based high throughput model to enable studies on molecular processes and to discover targets for the development of drugs for osteoarthritis. With globally >300 million patients and no available cure it can be foreseen that an effective intervention created using our model has the potential for rapid penetration in the market.

In summary,  based on the changes in molecular profile of hypertrophic chondrocytes in osteoarthritic cartilage, we identified drugs that are already used for other diseases, that could potentially reverse the phenotypical changes in these hypertrophic chondrocytes. To test these drugs we used several culture models using cartilage from patients; this includes a new model system that allows us to do faster screening of potentially interesting drugs or drug targets. In addition we have developed new culture models to better study the changes that happen in the cartilage during osteoarthritis. The models provided interesting clues to the role of the thin layer of calcified cartilage, certain type of macrophages and endothelial cells and these models can be used to identify and test more potential drug targets in the future.

Summary
Many people suffer from pain and disability due to osteoarthritis. Osteoarthritis is caused by the loss of cartilage in a joint. We aim to understand the very first changes in the behaviour of cells in the cartilage, before tissue damage is visible. This knowledge will be used to develop treatments.
Technology Readiness Level (TRL)
1 - 4
Time period
33 months
Partners
Logo
Logo