Osteoarthritis (OA) is the most common adult joint disease, increasing in frequency and severity in all aging populations. The estimated U.S. prevalence is 20-40 million patients or 5 times that of rheumatoid arthritis. The most common forms of OA involve the hand, knee, hip and spine. Total knee replacements number over 600,000 per year and total hip replacements number over 250,000 per year in the United States. OA may involve a single joint or multiple joints in the same individual, with current therapy focused on pain relief, as there is no FDA-approved therapy that arrests or reverses the joint deterioration. The etiology of OA is multi-factorial involving both mechanical and biochemical factors. OA progression is associated with accelerated cartilage degradation leading to joint space narrowing (JSN), painful joint disruption, and functional compromise. The pattern of manifestation of OA in many ways mimics that of osteoporosis in that it is more common in women than in men, and it appears to be related to postmenopausal changes with hormone replacement therapy suppressing cartilage degradation. OA disease progression is characterized by a pro-inflammatory gene expression pattern in cartilage and in joint synovial fluid, with a reactive increase in bone density in the subchondral bone. Large amounts of data provide support for a central role of interleukins in the pathogenesis of OA including animal susceptibility models, models of IL-1-targeted therapy, genetic association studies, and elevated interleukin gene expression in patients with generalized OA. Genetic variations in the interleukin gene cluster have been previously determined to be associated with multiple clinical phenotypes in OA. Our OA program plans to investigate if interleukin gene variations together with several other inflammatory gene variations are associated with progression of OA for the development of a genetic risk assessment test.
Interleukin Genetics has recently reported new findings on the genetics of OA at the World Osteoarthritis Congress in 2008 and at the American College of Rheumatology Annual Meeting in 2010. We reported that a panel of genetic markers was highly predictive of which knee OA patients were likely to develop severe disease as they age. The studies were done as collaborations between the Company and New York University Hospital for Joint Diseases and the University of North Carolina at Chapel Hill. These findings were similar in two studies. This information allows pharmaceutical companies that are developing the first disease-modifying drugs for OA (DMOADs) to screen patients and include in their clinical trials only those patients who have progressive disease. There is currently no mechanism for selecting high risk patients, and multiple clinical DMOAD studies have failed due to excessive numbers of patients with no progression of disease. This genetic information will also assist the rheumatologist in managing the medical and surgical options of individual patients. Additional studies identified a different set of genetic markers that were predictive of which patients started with knee OA and subsequently developed hand problems. We have recently published data that validates the use of the test to identify knee OA patients who are more likely to progress to severe disease and complications (Wu et al. 2013). We intend to search for marketing and sales partners to introduce the tests in the medical channel.