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Biotech / Medical : Neurocrine Biosciences (NBIX) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (987)	10/7/2002 8:58:03 PM
From: Miljenko Zuanic	Read Replies (2) \| Respond to of 1834

Are we at point when another setback for NBIX APL technology is for real? jci.org J. Clin. Invest. 110:1021-1027 (2002). doi:10.1172/JCI200215488. Copyright ©2002 by the American Society for Clinical Investigation -------------------------------------------------------------------------------- Article Anti-peptide autoantibodies and fatal anaphylaxis in NOD mice in response to insulin self-peptides B:9-23 and B:13-23 Edwin Liu1,2, Hiroaki Moriyama1, Norio Abiru1, Dongmei Miao1, Liping Yu1, Robert M. Taylor1, Fred D. Finkelman3 and George S. Eisenbarth1 1 Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, USA 2 Section of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital, University of Colorado Health Sciences Center, Denver, Colorado, USA 3 Division of Immunology, University of Cincinnati College of Medicine, Cincinnati Veterans Administration Medical Center, and Children’s Hospital Medical Center, Cincinnati, Ohio, USA Address correspondence to: George S. Eisenbarth, 4200 East Ninth Avenue, Box B140, Denver, Colorado 80262, USA. Phone: (303) 315-4891; Fax: (303) 315-4892; E-mail: George.Eisenbarth@uchsc.edu. Received for publication March 20, 2002, and accepted in revised form August 6, 2002. There is evidence that amino acids 9–23 of the insulin B chain are a major target of anti-islet autoimmunity in type 1 diabetes. Administration of this peptide to NOD mice prevents diabetes, and phase I trials of an altered peptide ligand of B:9-23 are underway in humans. We were interested in long-term subcutaneous therapeutic administration of B:9-23 without adjuvant. To our initial surprise, the peptide consistently induced fatal anaphylaxis in NOD mice after 6 weeks of administration. Anaphylaxis could be blocked by a combination of antihistamine and platelet-activating factor antagonist (but neither alone) or by a combination of anti–IgG receptor and anti-IgE antibodies. High titers of anti–B:9-23 antibodies were induced within 3–4 weeks of immunization with the peptide. Peptide B:13-23 also induced anaphylaxis and was more potent than peptide B:9-23. Antibodies induced by peptide B:9-23 and peptide B:13-23 did not cross-react with each other. Thus, the insulin peptides B:9-23 and B:13-23, even when administered subcutaneously in the absence of adjuvant, can induce a dramatic humoral response leading to fatal anaphylaxis in NOD mice