o-(chloroacetylcarbamoyl)fumagillol and Synovitis

Angiogenesis inhibition, long studied in the treatment of malignancies, has begun to emerge as a potential therapeutic approach in managing inflammatory arthritis, particularly rheumatoid arthritis. The growth of new vessels is required for the development of the rheumatoid pannus, which then leads to extensive synovial inflammation and joint destruction. Vascular endothelial growth factor is the best studied mediator of angiogenesis, and several therapies have been developed that specifically target this molecule. Several other angiogenesis mediators, such as the angiopoietin-TIE system, hypoxia inducible factor and integrin alpha(V)beta(3), as well as naturally occurring inhibitors of angiogenesis, are also being investigated as potential therapeutic targets. Additionally, there are a number of drugs, including paclitaxel, 2-methoxyestradiol and fumagillin analogs, that might have a role in inhibiting angiogenesis and, thus, in treating proliferative synovitis.

Topics: Angiopoietins; Cyclohexanes; Epoxy Compounds; Fatty Acids, Unsaturated; Humans; Hypoxia-Inducible Factor 1; Integrin alphaVbeta3; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Receptor, TIE-2; Sesquiterpenes; Synovitis; Tubulin Modulators; Valine; Vascular Endothelial Growth Factor A

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that occurs two to four times as often in women as in men and increases in incidence with advancing age. It affects synovial-lined joints and can also affect the pulmonary, cardiac, nervous, integumentary, and reticuloendothelial systems. RA is manifested clinically by malaise and fatigue, followed by a symmetric pattern of joint inflammation characterized by pain and stiffness. RA most likely occurs in the setting of a genetically predisposed individual, triggered by infectious agents or endogenous antigens. Many of the newer treatments being studied involve blocking cytokine-mediated interactions between cells of the synovium.

Topics: Aged; Antibodies, Monoclonal; Arthritis, Rheumatoid; Cyclohexanes; Diphtheria Toxin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Herpesvirus 4, Human; Humans; Interferon-gamma; Interleukin 1 Receptor Antagonist Protein; Interleukin-2; Lymphocyte Activation; Male; Methotrexate; Minocycline; Neoplasm Proteins; O-(Chloroacetylcarbamoyl)fumagillol; Parvoviridae; Receptors, Tumor Necrosis Factor, Type II; Recombinant Fusion Proteins; Sesquiterpenes; Sialoglycoproteins; Synovitis; Tumor Necrosis Factor Decoy Receptors