Metalloproteinase inhibitors: new opportunities for the treatment of rheumatoid arthritis and osteoarthritis.
The clinical efficacy of anti-TNF-alpha therapies have highlighted the apparently central role that TNF-alpha plays in the pathology of rheumatoid arthritis, particularly the inflammatory component. Recent identification of a metalloproteinase from the metzincin superfamily responsible for the production of the soluble form of this cytokine, has generated a large amount of pharmaceutical interest and presents the prospect of a metalloproteinase inhibitor as an anti-inflammatory drug. However, the traditional focus of metzincin inhibitor research has been the identification of inhibitors of matrix metalloproteinases; enzymes associated with matrix destruction, a feature common to both rheumatoid arthritis and osteoarthritis. Inhibitors of this class of metalloproteinase are now in clinical evaluation in patients. This review summarises the current development status of metalloproteinase inhibitors in arthritic diseases and discusses some of the issues that have arisen during their progress to become clinical treatments for these diseases.
Shaw
T
T
Roche Products Ltd., 40 Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AY, UK.
Nixon
J S
JS
Bottomley
K M
KM
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010003:Osteoarthritis / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology
D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases