Methods and formulations for treating or preventing Vascular Cognitive Impairment (VCI) through mucosal administration of E-selectin, an inducible adhesion molecule on endothelial cells

Available for licensing are methods and formulations for treating or preventing Vascular Cognitive Impairment (VCI) through mucosal administration of E-selectin, an inducible adhesion molecule on endothelial cells. Vascular dementia is defined as the loss of cognitive function resulting from ischemic, ischemic- hypoxic, or hemorrhagic brain lesions as a result of cerebrovascular diseases and pathologic changes. Presently no adequate medical treatment exists for VCI. Cerebrovascular disease causes proinflammatory cytokines such as IL-1 and TNF to induce the expression of E-selectin on human endothelium. E-selectin mediates the adhesion of various leukocytes, including neutrophils, monocytes, eosinophils, natural killer cells, and a subset of T cells to the activated endothelium. Activation of vascular endothelial cells by proinflammatory cytokines is believed to be involved in conversion of the luminal surface of endothelium from anticoagulant and anti-inflammatory to procoagulant and pro-inflammatory. These vascular changes are thought to underlie the development of VCI. Mucosally administered antigens can inhibit immune responses in an antigen specific fashion by inducing a subset of lymphocytes to produce anti-inflammatory cytokines in the presence of the antigen. This type of tolerance has been termed "bystander suppression". In an animal model of VCI, intranasal administered E-selectin suppressed activation of vessel segments beginning to express E-selectin and thus prevented the development of VCI. Immunosuppression via antigen-specific modulation of the immune response (mucosal tolerance) should have no systemic immunosuppressive effects.

U.S. Provisional Application No. 60/712,359 filed 30 Aug 2005 (HHS Reference No. E-271-2005/0-US-01) Inventors: John M. Hallenbeck et al. (NINDS)

Licensees sought: Available for non-exclusive or exclusive licensing. Collaborative Research Opportunity: The NINDS Stroke Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of E-selectin for treatment of VCI. For more information, please contact: Laurie Arrants, NINDS Technology Transfer Office, 301-435-3112; arrantsl@ninds.nih.gov.