NEW YORK, Dec. 14, 2012 (GLOBE NEWSWIRE) -- Synergy Pharmaceuticals Inc. (Nasdaq:SGYP), a developer of new drugs to treat gastrointestinal disorders and diseases, today announced that a poster presentation on SP-333, Synergy's next-generation guanylate cyclase-C (GC-C) agonist to treat ulcerative colitis, will be made at the 2012 Advances in Inflammatory Bowel Diseases, Crohn's & Colitis Foundation's Clinical & Research Conference. The conference takes place December 13-15 at the Westin Diplomat in Hollywood, FL.
The poster describes animal studies showing that oral treatment with SP-333, an analog of uroguanylin, ameliorated gastrointestinal (GI) inflammation in dextran sodium sulfate (DSS) induced colitis in mice, and that down-regulation of NF-kB and pro-inflammatory cytokines was associated with SP-333 administration. The data also demonstrate that systemic absorption of orally administered SP-333 is minimal, and is unaffected by the severity of the experimental colitis. Synergy recently completed a single-dose, dose-escalating Phase I trial of SP-333 in healthy adult volunteers, and is planning to initiate a multi-dose, dose-escalation study in healthy volunteers in early 2013.
Recent studies suggest that expression of uroguanylin, the native GC-C agonist expressed in the human GI tract, is down-regulated in inflamed tissue from patients with Crohn's disease and in patients with ulcerative colitis, implying that uroguanylin deficiency may be associated with disruption of intestinal barrier function, one of the primary hypothesized causes of the pathogenesis of inflammatory bowel disease."Oral treatment with SP-333 to augment intestinal GC-C activation may represent a novel approach for restoring mucosal barrier function and suppressing inflammation," said Dr. Kunwar Shailubhai, Chief Scientific Officer of Synergy Pharmaceuticals, Inc. "In experimental models of colitis in mice, treatment with SP-333 ameliorates GI inflammation possibly through inhibition of NF-kappa B signaling to suppress production of pro-inflammatory cytokines." The poster: SP-333, a Guanylate Cyclase-C Agonist, Ameliorates DSS-colitis in Mice via a Novel Cyclic GMP-Mediated Mechanism (P-198), authored by Kunwar Shailubhai, John Foss, Graham Zhang, Krishna P Arjunan, Rong Feng, Stephen Comiskey, Gary S. Jacob, and Scott E. Plevy, will be presented by Dr. Shailubhai on Friday December 14 between 6 PM and 7PM at the Westin Diplomat in Hollywood, FL. About SP-333 SP-333 is a synthetic analog of uroguanylin, a natriuretic hormone which is normally produced in the body's intestinal tract. Deficiency of uroguanylin is likely to be one of the primary reasons associated with formation of polyps as well as debilitating and difficult-to-treat GI inflammatory disorders such as ulcerative colitis and Crohn's disease. Orally-administered SP-333 binds to and activates guanylate cyclase C (GC-C) expressed on epithelial cells lining the GI mucosa, resulting in stimulation of cyclic GMP in target tissues. Its enhanced stability makes this peptide an extremely potent GC-C agonist in animal studies in mice and monkeys, promoting bowel movement in monkeys, and ameliorating GI inflammation in mice, respectively.