152 153 Intestinal Disease Meeting Berlin 2006 - Dr. Falk Pharma ...

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Session 5 New Therapeutic Approaches (Part I) Chair: W.J. Sandborn, Rochester E.F. Stange, Stuttgart 42 The search for new therapy concepts Because the currently available therapeutic options do not help all IBD patients, the search for new therapeutic concepts continues with heightened intensity. Researchers are focusing on promising concepts such as immunostimulating DNA sequences (ISS) and on synthetic oligonucleotides which, said D. Rachmilewitz (Jerusalem) inhibit apoptosis in the epithelial cells of the colon (figure 29). In experimental models of colitis, ISS possess pronounced anti-inflammatory properties, making these DNA sequences attractive Fig. 29 naive D. Rachmilewitz A. Sturm target structures for the development of new therapeutic agents for IBD. Another promising therapy concept, said A. Sturm (Berlin) is represented by the probiotics, which appear to inhibit the release of proinflammatory cytokines. “Probiotics reduce disease activity,” A. Sturm said. As evidence, he cited three double-blind placebo-controlled studies in patients with ulcerative colitis, in which the active agent successfully maintained remission. Probiotics could therefore be a possible alternative to mesalazine in patients who do not tolerate this medication. DSS DSS & M-ODN DSS & ISS-ODN ISS-ODN = immunostimulatory sequence oligodinucleotides M-ODN = methylated oligodinucleotides DSS = dextran sulfate sodium I ISS-ODN inhibits DSS-induced apoptosis of colonic epithelium (D. Rachmilewitz, Jerusalem)
Promising results with helminths The observation that IBD occurs almost exclusively in industrial nations and much less frequently in the developing world may also contribute to the development of new therapy concepts. “The pathogenesis of these diseases also appears to have something to do with the standard of hygiene,” said J.V. Weinstock (Boston). Observations in mice that animals exposed to certain worms of the helminth group appeared to be protected against inflammation in the colon led to the effort to establish this principle in humans. According to J.V. Weinstock, the helminths may Fig. 30 J.V. Weinstock R.W. Summers 2. Larvae released 1. Ingestion Infective ova Ingested 3. Mucosal attachment Penetrate and develop in mucosa Internal Embryonated egg (infective stage) External I Trichuris suis life cycle (R.W. Summers, Iowa City) Congress Short Report Falk Symposium trigger immune reactions, such as the release of IL-12 and IFN-γ. Meanwhile the first clinical studies on humans treated with helminth (Trichuris suis) ova (figure 30) report a reduction in disease symptoms. Very promising were the results of a pilot study of 54 patients with ulcerative colitis presented in Berlin by R.W. Summers (Iowa City). Patients were treated with Trichuris suis ova, with 45% of patients responding to therapy. The difference with respect to placebo was not initially significant but became so after six weeks. Over the twelveweek treatment a total of 60% of patients responded positively to treatment with helminth ova compared to 12% showing improvement on placebo. There are also first reports of therapeutic efficacy in patients with Crohn’s disease. In one study, 29 patients were treated, of whom 65% achieved remission within twelve weeks, with a total of 76% of patients showing a clear clinical response. Side effects and serious complications were not observed. Cell Eggs in feces (diagnostic stage 4. Maturation 5. Egg excretion(noninfective) 6. Embryonation in soil 153 43
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