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. 2001 Nov;60(Suppl 3):iii62–iii67. doi: 10.1136/ard.60.90003.iii62

Matrix metalloproteinase inhibitors in rheumatic diseases

D Close
PMCID: PMC1766680  PMID: 11890658

Abstract

The rheumatic diseases continue to represent a significant healthcare burden in the 21st century. However, despite the best standard of care and recent therapeutic advances it is still not possible to consistently prevent the progressive joint destruction that leads to chronic disability. In rheumatoid arthritis and osteoarthritis this progressive cartilage and bone destruction is considered to be driven by an excess of the matrix metalloproteinase (MMP) enzymes. Consequently, a great number of potent small molecule MMP inhibitors have been examined. Several MMP inhibitors have entered clinical trials as a result of impressive data in animal models, although only one MMP inhibitor, Ro32-3555 (Trocade), a collagenase selective inhibitor, has been fully tested in the clinic, but it did not prevent progression of joint damage in patients with rheumatoid arthritis.
  The key stages and challenges associated with the development of an MMP inhibitor in the rheumatic diseases are presented below with particular reference to Trocade. It is concluded that the future success of MMP inhibitors necessitates a greater understanding of the joint destructive process and it is hoped that their development may be accompanied with clearer, more practical, outcome measures to test these drugs for, what remains, an unmet medical need.



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Figure 1  .

Figure 1  

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Prevention of joint damage by the MMP inhibitor, Trocade: magnetic resonance imaging of the rabbit knee P acnes model. (A) Normal control; (B) arthritic control, illustrating cartilage/bone damage and synovitis; (C) arthritic knee + Trocade, illustrating protection of cartilage/bone despite synovitis.

graphic file with name ard-medm.f1.jpg

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Selected References

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