Mig Inhibition of Eosinophils
Background
- Eosinophils are granulocytic leukocytes normally present in low numbers in peripheral blood and their presence in tissues is normally restricted to gastrointestinal mucosa.
- The primary function of eosinophils is in defense against invading organisms.
- Several disease states including allergic disorders, asthma, eosinophilic gastroenteritis, and hypereosinophilic syndrome are associated with increased numbers of eosinophils in blood and/or tissues.
- Th2 cytokines, especially IL-5, control the proliferation and differentiation of eosinophils. Eosinophil accumulation is controlled by a variety of chemokines, including the eotaxins which interact with the eosinophil-specific CCR3 receptor.
- Activated esoinophils release toxic enzymes and induce the synthesis of inflammatory mediators, killing invading organisms but also resulting in local tissue damage. In eosinophilic diseases, increased numbers of eosinophils cause tissue damage and disease progression.
- Methods to control the proliferation and/or trafficking of eosinophils in these diseases are thus of therapeutic value.
Description of Current Technology
Dr. Marc Rothenberg and colleagues at Cincinnati Children's Research Foundation discovered that Mig (monokine induced by interferon), a chemokine induced by Th1 cells, inhibited both eosinophil recruitment and effector function in a mouse model of lung allergy1. Intravenous administration of microgram levels of Mig prior to IL-13 or allergen stimulation inhibited eosinophil migration to lung tissue. Pretreatment of mice with Mig inhibited eotaxin induced eosinophil migration to the lung, demonstrating that Mig specifically interferes with CCR3 ligand induced functions. Pretreatment with Mig also inhibited eotaxin induced mobilization of eosinophils to blood. In isolated eosinophils, Mig caused decreased superoxide production in response to eotaxin, demonstrating that Mig regulates eosinophil effector function. Mig inhibits eosinophil responses to both CCR3 and non-CCR3 ligands through negative signaling via the CCR3 receptor. Its ability to regulate both eosinophil recruitment and effector function suggests novel therapeutic applications of Mig in a variety of eosinophil mediated diseases including asthma, allergy and eosinophilic syndromes.
1)Fulkerson PC et al, Proc. Natl. Acad. Sci. 101:1987-92 (2004).
Objective
Cincinnati Children's Research Foundation is seeking a commercial partner for the development and commercialization of this technology as a novel therapy for eosinophil mediated diseases. A license or option agreement is available. A patent application has been filed.
Contact
We welcome inquiries concerning this technology. To receive further confidential information, please contact:
Joseph D. Fondacaro, PhD
Director, Office of Intellectual Property and Venture Development
Cincinnati Children's Research Foundation
Mail Location 7032
3333 Burnet Avenue
Cincinnati, OH 45229-3039
Phone: 513-636-7695
Fax: 513-636-8453
Email: jdfonda@cchmc.org
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