The pathogenesis of many chronic and acute diseases of man has been demonstrated to have substantial involvement of cellular adhesion molecules known as selectins. The selectins mediate leukocyte recruitment into tissue sites to promote inflammatory injuries that underlies septic shock, ischemia-reperfusion injury, acute respiratory distress syndrome, and various chronic immune allergic disorders such as asthma and psoriasis. The goal of this project is to establish efficacy and safety data for potent selectin inhibitors to attract venture capital and/or a pharmaceutical partner to advance the PLN therapeutics through Phase I and II clinical trials. Through preliminary Phase I study the investigators have demonstrated that a defined group of multimerized selectin ligand analog expresses on UV-stabilized lyposomes termed PLN are very effective as selectin inhibitors in human cell shear assays systems and in mice. In this Phase II proposal the investigators seek to optimize the formulation and synthesis of PLN based therapeutics for comprehensive studies of animal models of human asthma and psoriasis in collaboration with the University of Michigan. These studies will serve as the basis for the toxicological and phramacokinetic studies that will serve to prepare PLN therapeutics for filing an IND/CTX.
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| John, Alison E; Lukacs, Nicholas W; Berlin, Aaron A et al. (2003) Discovery of a potent nanoparticle P-selectin antagonist with anti-inflammatory effects in allergic airway disease. FASEB J 17:2296-8 |
