A SMALL MOLECULE DRUG EFFICIENTLY TREATS ARTHRITIS IN ANIMAL MODELS

Background: Most current treatment concepts for rheumatoid arthritis non-specifically suppress immune responses, cause numerous side effects and are not curative.Results: We could show that our small molecule compound BX-1, which targets enzymes involved in glucocorticoid metabolism, efficiently and without overt side effects inhibits experimental arthritis or induces remission in two different rat models. Adjuvant induced arthritis (mycobacterium tuberculosis in IFA) is a monophasic and antigen dependent disease, whereas pristane induced arthritis represents a chronic disease induced by mineral oil only. BX-1 could be given either preventively at the time of arthritis induction, or even therapeutically at onset of clinical disease symptoms. Furthermore, BX-1, although applied three times only, conferred long lasting protection in both models. This is in striking contrast to other treatments, which cannot be discontinued without disease exacerbation. Most importantly, BX-1 not only inhibited inflammation of all joints and improved the overall well being as demonstrated by a total block of weight loss, it also greatly reduced bone and cartilage erosion.The novel treatment concept of targeting endogenous glucocorticoid metabolism seems to allow for immunomodulation rather than immunosuppression. It reduces the likelihood of side effects and avoids the risk of infection.Conclusion: BX-1's efficiency to treat arthritis in two animal models which both resemble human rheumatoid arthritis in different ways makes it an excellent lead candidate for the development of new drugs for the treatment of arthritis patients.Citation: , volume , supplement , year 2004, page Session: Rheumatoid arthritis – Etiology and pathogenesis/Animal models