PARASITE-DERIVED INHIBITORS OF LEUKOCYTIC OXIDANT BURST

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DESCRIPTION: Inotek Corporation, a Massachusetts-based biopharmaceutical small business, has joined with Antibody Systems to research and develop parasite-derived anti-inflammatory molecules that may be useful as novel therapeutics for auto-immune disease. The purpose of this proposal is to test the in vivo feasibility of candidate parasite extracts that have proven to be effective in vitro in blocking the PMN oxidant burst. They will focus in this scope of work on a specific experimental model of sub-acute regional immune-mediated intestinal inflammation. They will test this hypothesis in a rat model of enterocolitis, produced by colonic instillation of the hapten trinitrobenzene sulfonic acid in ethanol. This well-established model faithfully reproduces many of the features of clinical IBD. Parasite extracts will be administered in a randomized double-blinded protocol for 8 days. They expect that a successful candidate for further development will reduce tissue lipid peroxidation, improve gross appearance of the colonic mucosa, decrease histologic inflammatory activity score, and reduce weight loss. Extracts which appear promising in an initial screening will be further tested for dose-dependent relief of experimental colitis. The results of the present application will permit application for Phase II SBIR funding to support the isolation, purification, identification, and synthesis of the active principle(s) of parasite extracts that inhibit the PMN oxidant burst. These tasks would necessarily be followed by pre-clinical pharmaceutical testing (advanced toxicity determinations, pathology, immunogenicity, stability, pharmacokinetics, in vivo efficacy), an investigational drug application to the FDA, and a Phase I clinical trial for the treatment of clinical indications characterized by inflammatory injury. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE