Motile Sperm Domain Containing Protein 2 and Inflammation

Abstract

Disclosed herein are methods of treating, preventing, or reducing the incidence of an inflammatory disease or disorder and methods of inhibiting, preventing, or reducing the incidence of one or more activities in a cell with an inhibitor of a Motile Sperm Domain containing Protein 2 (MOSPD2). Also disclosed are inhibitors of MOSPD2 and pharmaceutical compositions containing MOSPD2 inhibitors.

Description

FIELD OF THE INVENTION[0001]This invention relates to anti-inflammatory processes, for example, methods of treating, preventing, or reducing the incidence of one or more activities in a cell, or one or more inflammatory diseases or disorders with an inhibitor of Motile Sperm Domain containing Protein 2 (MOSPD2). The invention also relates to pharmaceutical compositions comprising one or more inhibitors of MOSPD2.BACKGROUND OF THE INVENTION[0002]Leukocytes are the cells of the immune system that are involved in defending the body against infectious disease and foreign materials. Monocytes are a type of leukocytes and have critical roles in innate and adaptive immunity, immune surveillance, and particle scavenging. While a subset of monocytes is “resident” and recruited to tissues independently of inflammatory stimuli to assist in steady-state surveillance, wound-healing and resolution of inflammation, the majority (80-90%) of human circulating monocytes are classified as “inflammator...

AI Technical Summary

Benefits of technology

[0007]The present invention, in some embodiments, relates to methods of treating, preventing, or reducing the incidence of an inflammatory disease or disorder with an inhibitor of Motile Sperm Domain containing Protein 2 (MOSPD2), and to methods of inhibiting or preventing one or more activities in a cell with an inhibitor of MOSPD2. In some embodiments, the invention relates to various methods of treatment or prevention, including methods of treating, preventing, or reducing the incidence of an inflammatory disease or disorder, comprising administering to a subject in need thereof a therapeutically effective amount of an inhibitor of MOSPD2. In other embodiments, the invention relates to a method of inhibiting, preventing, or reducing the incidence of one or more activities in a cell, comprising administering to a subject in need thereof a therapeutically effective amount of an inhibitor of MOSPD2, wherein the one or more activities is one or more of: MOSPD2 expression, inflammatory cell migration (e.g., leukocyte or monocyte migration), chemotaxis (e.g., leukocyte or monocyte chemotaxis), a chemokine signaling pathway, ERK phosphorylation and AKT phosphorylation. In some embodiments, the inhibitor of MOSPD2 is an antibody or antigen binding fragment thereof. In other embodiments, the antibody is a polyclonal, monoclonal, murine, human, humanized, or chimeric antibody. In some embodiments, the invention relates to various methods of inhibiting MOSPD2 in a cell, comprising contacting the cell with an effective amount of an inhibitor of MOSPD2.

[0008]In some embodiments, the inhibitor of MOSPD2 is a small molecule, such as an oxidized phospholipid. In one preferred embodiment, the inhibitor of MOSPD2 is VB-201. In some embodiments, the inhibitor of MOSPD2 is an inhibitor of MOSPD2 that is not an oxidized phospholipid. In some embodiments, the inhibitor of MOSPD2 is an inhibitor of MOSPD2 that is not VB-201. In some embodiments, the inhibitor of MOSPD2 binds to MOSPD2 expressed on a cell surface (e.g., an inflammatory cell surface).

[0009]In other embodiments, the invention also relates to polypeptides that inhibit MOSPD2 and pharmaceutical compositions containing a polypeptide that inhibits MOSPD2. In some embodiments, the polypeptide is an antibody or antigen binding fragment thereof.

[0010]In some embodiments, the antibody or antigen binding fragment thereof specifically binds to MOSPD2. In other embodiments, the antibody or antigen binding fragment thereof binds to MOSPD2 with an equilibrium dissociation constant (KD) of from about 10−6 M to about 10−12 M. In other embodiments, the MOSPD2 is human MOSPD2. In

Problems solved by technology

Nevertheless, there have been several phase II clinical trial failures with chemokine and chemokine receptor antagonists, possibly due

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