Use of E-Selectin Tolerization as Treatment for Immunological and Vascular-Related Disorders
Posted May 14 2012 8:00pm
Description of Invention: This technology relates to the mucosal delivery (e.g. intranasal) of an E-selectin fragment as a tolerization agent for the prevention and treatment of immunological and vascular-related disorders, including stroke and multiple sclerosis (MS) as well as rare or orphan diseases involving vascular modulated disorders.
E-selectin is an adhesion molecule that is expressed on endothelial cells lining blood vessels in response to certain localized cytokines, making the endothelial surface pro-coagulant, pro-inflammatory and/or immunoreactive. Such changes on the endothelial surface have been linked to the development of vascular-related disorders like stroke, as well as immune regulated diseases such as MS.
Intranasal administration of E-selectin, using a tolerizing dosing schedule, induces an immunological tolerance to E-selectin. T regulatory cells become targeted to activating blood vessel segments, where they release immunomodulatory cytokines such as IL-10. This release of cytokines suppresses local pro-coagulant, pro-inflammatory and immunoreactive effects. Thus, administration of E-selectin as a tolerizing agent will provide a targeted therapeutic approach, impacting only affected sites in the endothelium.
Applications: Treatment of diseases biologically based on vascular initiated immune regulation. Such disorders include prevention of secondary stroke, MS, Alzheimer’s, Parkinson’s, rheumatoid arthritis, type 1 diabetes, and psoriasis.
Low doses utilized thus minimizing potential side effects.
Animal data are available, with further studies currently on-going.
Administration through the intranasal route represents a less invasive mode of delivery.
FDA pre-IND meetings have been held and FDA communications are ongoing.
In vitro data available
In vivo data available (animal)
Inventors: John M Hallenbeck (NINDS) Maria Spatz (NINDS) Hidetaka Takeda (NINDS) Hideaki Wakita (NINDS)
Patent Status: HHS, Reference No. E-237-1999/0 US, , Patent No. 7,261,896, Issued 28 Aug 2007 US, Application No. 11/820,326 filed 19 Jun 2007 US, , Patent No. 7,897,575, Issued 01 Mar 2011 US, Application No. 12/859,048 filed 18 Aug 2010
and Foreign counterparts in Australia, Canada, Europe, and Japan
Collaborative Research Opportunity: The Stroke Branch, NINDS/NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the applications of E-selectin tolerization in treatment of neurological based disease. For collaboration opportunities, please contact Laurie Arrants, NINDS at firstname.lastname@example.org .
For Licensing Information Please Contact: Tara Kirby Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-435-4426 Fax: 301-402-0220