Abstract: This invention provides methods and compositions for inhibiting, reducing or slowing inflammatory diseases, for reducing sequestration or collecting or localization of macrophages, for treating a disease caused all or in part by or characterized by inflammation, for inhibiting, slowing, reversing or preventing atherosclerosis, and for increasing insulin sensitivity, decreasing or inhibiting resistance to insulin, or treating diabetes by inhibiting the biological activity of or antagonizing an axonal guidance protein. The method may feature administering a therapeutically effective amount of an agent to reduce or inhibit the biological activity of an axonal guidance protein or a receptor, analog, derivative or combination thereof.

Abstract: The invention provides methods and compositions for inhibiting, reducing or slowing inflammation or inflammatory arthritis, for treating inflammatory arthritis such as rheumatoid arthritis, psoriatic arthritis, and a spondyloarthropathy, for inhibiting, reducing or slowing osteoclast differentiation, function, or biological activity, for inhibiting or reducing persistence or accumulation of macrophages at an inflamed site or in an inflamed tissue or for promoting or increasing the efflux of macrophages from an inflamed site or an inflamed tissue, for increasing, stimulating, or promoting lymphocyte cell adhesion, for increasing, stimulating, or promoting lymphocyte efflux from a site of inflammation or from an inflamed tissue, and for decreasing, inhibiting, or reducing a lymphocyte cellular response by inhibiting, inhibiting the biological activity of or antagonizing an axonal guidance protein or a receptor thereof. The axonal guidance protein may be a netrin such as netrin-1, and its receptor may be unc5b.

Abstract: The invention provides methods and compositions for reducing or inhibiting osteolysis, bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that inhibits the biological activity of an axon guidance protein. The compound or agent my inhibit transcription or translation of or bind to an axon guidance protein, such as, for instance, a netrin like netrin-1. Likewise, the compound or agent may inhibit transcription or translation of or bind to a receptor of an axon guidance protein, such as, for instance, a netrin receptor such as unc5b. In some instances, the compound or agent is an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such compounds and agents.

Abstract: The inhibition of miRNA miR-33 is shown to promote the polarization of macrophages from an M1 to an M2 phenotype. MiR-33 inhibitors are therefore useful for treating inflammation in subjects. Endogenous microRNAs can be silenced using antagomirs. The miR-33 inhibitor is preferably an antagomir having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

Abstract: The invention provides methods and compositions for inhibiting, reducing or slowing inflammation or inflammatory diseases, for reducing sequestration or collecting or localization of macrophages, for treating a disease caused all or in part by or characterized by inflammation such as, for instance, chronic inflammation, for inhibiting, slowing, reversing or preventing atherosclerosis, and for increasing insulin sensitivity, decreasing or inhibiting resistance to insulin, or treating diabetes by inhibiting, inhibiting the biological activity of or antagonizing an axonal guidance protein. The methods may feature administering to a subject a therapeutically effective amount of an agent effective to inhibit or reduce the biological activity of an axonal guidance protein or a receptor of the axonal guidance protein, or an analog, derivative or combination thereof.

Abstract: The invention provides methods and compositions for reducing or inhibiting osteolysis, bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that inhibits the biological activity of an axon guidance protein. The compound or agent my inhibit transcription or translation of or bind to an axon guidance protein, such as, for instance, a netrin like netrin-1. Likewise, the compound or agent may inhibit transcription or translation of or bind to a receptor of an axon guidance protein, such as, for instance, a netrin receptor such as unc5b. In some instances, the compound or agent is an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such compounds and agents.

Abstract: The inhibition of miRNA miR-33 is shown to promote the polarization of macrophages from an M1 to an M2 phenotype. MiR-33 inhibitors are therefore useful for treating inflammation in subjects. Endogenous microRNAs can be silenced using antagomirs. The miR-33 inhibitor is preferably an antagomir having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

Abstract: The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

Abstract: The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.