Washington University

Other

Novo Nordisk A/s

Cosmo Research & Development S.p.a.

Cosmo Technologies Limited

Marco Colonna

Axel Bouchon

Vibeke Westphal Stennicke

Anette Henriksen

Charlotte Wiberg

Rune Salbo

Mette Dahl Andersen

Marina Celia

Amanda L Blasius

Marina Cella

Alexander David Barrow

Tyler Ulland

Cristiane Secca Da Silva

Yarning Wang

Among the various aspects of the present disclosure is the provision of methods of treating a microglial dysfunction-associated diseases, disorder, and conditions. The present disclosure provides for a method for treating microglial dysfunction in a subject having a microglial dysfunction-associated neurodegenerative disease comprising administering to a subject a therapeutically effective amount of a microglial rescuing agent. The present disclosure also provides for a method of reversing neuronal damage in a subject having a microglial dysfunction-associated neurodegenerative disease, wherein the microglial dysfunction-associated neurodegenerative disease is characterized by a single nucleotide polymorphisms (SNPs) or mutation in Trem2 or ApoE affecting microglial functions.

Methods for treating microglial dysfunction

The present invention is directed towards isolated antibodies that bind to IL12Rβ1. Specifically, anti-IL12Rβ1 antibodies, and methods of treatment using the antibodies are disclosed. The antibody is targeted against the beta 1 subunit of the receptors of IL-12 and IL-23 and is capable of blocking signaling by inflammatory cytokines IL-12 and IL-23, which could be useful in treating autoimmune inflammatory diseases, such as inflammatory bowel disease (IBD), RA, and psoriasis.

Anti-IL12RB1 antibodies

Among the various aspects of the present disclosure is the provision of methods and compositions for modulating the Natural Cyotoxicity Receptor 2 (NCR2).

Activation of natural cytotoxicity receptor 2 (NCR2)

The present invention provides TREM2 constructs. TREM2 constructs of the invention are polynucleotide sequences encoding a polypeptide, wherein the polypeptide comprises at least one TREM2 or fragment thereof and a targeting moiety and optionally comprising a signal peptide and/or a purification moiety. The present invention also provides isolated polypeptides encoded by TREM2 constructs, vectors comprising TREM2 constructs, isolated cells comprising said vectors, and methods of use thereof.

Compositions comprising TREM2 and methods of use thereof

Novel activating receptors of the lg super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-&#x3b2;. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Receptor TREM (triggering receptor expressed on myeloid cells) and uses thereof

An isolated and characterized monoclonal antibody ('440c') prepared by immunizing Wistar/CRL rats subcutaneously with purified rat bone marrow IPC, fusing popliteal lymph nodes of the rats with SP2/0 myeloma spleen cells and differentially selecting for hybridome supernatants that successfully stain bone marrow derived IPC and fractions thereof using CD11c+ spleen cells and, differentially selecting for hybridoma supernatants from the CD11c+ spleen cells that successfully stain only CD 11 c+/Ly6c+/CD 11 b&#x2212;/B220+ splenocytes to provide the monoclonal antibody.

Biologically active antibodies recognizing a cell surface molecule selectively expressed on living mouse natural type one (I) interferon producing cells

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-&#x3b2;. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Growing community of inventors

St. Louis, MO, United States of America

Marco Colonna