Novel therapeutic target identified in fight against Rheumatoid...( A team of scientists led by Toshihiro ...)

As published in the latest edition of Genes and Development, the scientists report the discovery of 'synoviolin', an enzyme that is found in abnormally high levels in diseased joints. High levels of synoviolin are found to cause an overgrowth of joint-destroying synovial cells, a key clinical feature of RA. By reducing levels of synoviolin, scientists hope to halt the proliferation of synovial cells and the devastating progression of RA.

RA is one of the most common joint diseases, affecting approximately 0.5-1.0% of the adult population worldwide. The progressive joint destruction, which mainly targets the small joints of the hands and feet, eventually results in severe movement disability. The clinical features of RA include chronic inflammation of the synovium, or lining of the joint, accompanied by the overgrowth of synovial cells, a condition known as synovial hyperplasia. This mass of synovial cells, or 'pannus', eventually invades and destroys the cartilage and bone within the joint. Clearly, understanding the factors that regulate synovial hyperplasia are key to designing new therapies to treat RA.

Dr Nakajima and colleagues set out to identify proteins found in synovial cells from rheumatoid joints, with the hope of discovering novel pathogenic factors involved in RA. Using an antibody screening approach, the scientists identified synoviolin as an enzyme that is upregulated in synovial tissues from RA patients. To elucidate the function of synoviolin, the team engineered mice that produced an excess of synoviolin. Significantly, these mice developed spontaneous arthritic joint disease, suggesting that too much synoviolin is indeed an important factor in the development of RA. They also gener
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
16-Sep-2003