Grant: Project Grant

Osteoarthritis (OA), the most common form of arthritis, is expected to affect 130 million people symptomatically worldwide and 40 million will be severely disabled by 2050. However, there is no cure for it yet. The biggest challenge to develop OA drugs is the wide heterogeneity of the disease. It is now recognized that OA is a nebula of several diseases, but we do not have markers to differentiate them yet. Several clinical classifications of OA have been proposed based on the OA risk factors and joint magnetic resonance imaging (MRI) assessment. These classifications improved our knowledge in the etiologies of OA but failed to subset the disease which results in inconsistent response to treatments. We performed metabolomic studies (study of small chemical compounds present in body fluids) on plasma and joint fluid samples obtained from OA patients and healthy controls and found at least three subtypes of OA characterized by different markers, implicating different metabolic pathways involved in OA. These markers have potential to be used to better stratify OA patients for clinical trials and developing personalized medicine tools. We now propose to confirm the findings and refine the markers and related pathways for each of the subtypes of OA by integrating genomics (study of all the genes) and metabolomics in three existing cohorts - the Newfoundland Osteoarthritis Study (NFOAS) as the discovery cohort (n=1113), the Longitudinal Evaluation in the Arthritis Program, Osteoarthritis Study (LEAP OA; n=900) and the Tasmania Older Adult Cohort Study (TASOAC; n=568) as the validation cohorts. The study will identify molecular subtypes of OA. It will help inform a better understanding of the etiologies of OA, provide tools to better stratify OA patients for clinical trials, and develop personalized medicine tools for OA management.