Millennium Pharmaceuticals discovers protein biomarkers that could play a role in the early detection of rheumatoid arthritis

Dec 14 2004

Researchers at Millennium Pharmaceuticals today announced the discovery of a panel of protein biomarkers that could play a role in the early detection, prognosis and monitoring of rheumatoid arthritis (RA).

The research, published in this month's Arthritis & Rheumatism in conjunction with an accompanying editorial, represents an important potential advance in the ability for clinicians to predict disease severity for patients with rheumatoid arthritis.

"The clinical application of these biomarkers could -- for the first time -- allow clinicians to identify patients who would benefit from aggressive treatment early enough in the disease course to prevent unnecessary joint destruction and disability," said Ronenn Roubenoff, M.D., senior director, Molecular Medicine, Millennium and a co-author of the study.

This study was conducted as part of a collaborative research alliance between Millennium and Roche Diagnostics. The researchers have selected 33 of these potential biomarkers for further validation in the serum of patients with RA as well as healthy volunteers.

To identify the biomarkers, researchers used a proteomic technique called mass spectrometry to generate and compare protein profiles of synovial fluids (joint fluids) from patients with erosive and non-erosive RA. The differences in the protein profiles revealed a distinct set of protein biomarkers that were elevated in the joint fluid of patients with erosive disease, but not in patients with non-erosive RA. Among the set of proteins more abundant in patients with erosive RA was C-reactive protein (CRP) and six members of the S100 protein family of calcium binding proteins. Many of the marker candidates discovered are directly or indirectly involved in cell signaling and inflammation.

Joint erosion is a standard clinical indication of future disability in RA. The identification of biomarkers that would predict erosion would allow physicians to identify patients who should receive aggressive anti-rheumatic treatment early in the hopes of preventing erosion and resulting disability.

"These are exciting discoveries that we are currently utilizing in our development and discovery efforts, such as incorporating the newly-identified biomarkers for treatment response into clinical studies designed to identify the right medicine for the right patients," said Roubenoff.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disease of the articular (rotating) joints that results in significant pain, stiffness and swelling and leads to degradation of the joint tissue. RA can cause permanent damage and deformities to joints, resulting in loss of function and ultimately leading to joint replacement surgery in some cases. In addition, some RA patients develop extra-articular manifestations such as rheumatoid nodules, interstitial lung disease and vasculitis.

According to the Arthritis Foundation, RA affects 2.1 million Americans and is about three times more common in women than men. The disease has a significant socioeconomic impact with medical costs and indirect expenses due to lost wages for RA estimated to be over $3 billion per year. In addition, mortality rates for people with RA are double those of the general population. The cause of RA is not known. However, it is believed that RA is an autoimmune disease where the body's natural immune system attacks healthy joint tissue causing inflammation and subsequent joint damage.