Composition comprising at least to compounds which induces indolamine 2,3 - dioxygenase (ido), for the treatment of an autoimmune disorder or suffering from immune rejection of organs

Abstract

A composition and method for using a composition, the composition having at least two compounds, each of which induces indolamine 2,3-dioxygenase, for the treatment of an autoimmune disorder or disease or immune rejection of transplants or gene therapeutically modified cells, wherein the inducers have different mechanism of action and wherein the composition gives rise to a synergistic effect on the IDO levels.

1 . A composition comprising at least two compounds which induces indolamine 2,3-dioxygenase (IDO), for the treatment of an autoimmune disorder or disease or suffering from immune rejection of organs, tissues, normal cells or gene therapeutically modified cells, wherein said IDO inducers have different mechanisms of action and give rise to a synergistic effect on the IDO level. 
     
     
         2 . The composition according to  claim 1 , wherein said inducers are selected from the group consisting of cytidine analogues, histone deacetylase inhibitors, vitamin D3 analogues, interferon gamma analogues, other interferons, toll like receptor ligands, gonadotropine receptor signalling hormones, prostaglandine E2 analogues, IDO stabilizers, soluble CTLA4 conjugates, and glycocorticoids. 
     
     
         3 . The composition according to  claim 2 , wherein said inducers are selected from the group consisting of cytidine analogues, histone deacetylase inhibitors, gonadotropine receptor signalling hormones, interferon gamma analogues, other interferons, and IDO stabilizers. 
     
     
         4 . The composition according to  claim 1 , wherein said inducers are selected from the group consisting of zebularine, valproic acid, human chorionic gonadotropine, interferon gamma, interferon A, and TGF-beta. 
     
     
         5 . The composition according to  claim 1 , wherein said composition comprising a pharmaceutically acceptable buffer, excipient, diluent, solvent or carrier. 
     
     
         6 . The composition according to  claim 1 , wherein said composition is used for the treatment of a disease selected from the group consisting of Achlorhydria, Acute hemorrhagic leukencephalitis, Addison's Disease, Alopecia Areata, Anemia, Pernicious Anti-Glomerular Basement Membrane Disease, Antiphospholipid Syndrome, Aplastic Anemia, Atopic Allergy, Autoimmune Atrophic Gastritis, Autoimmune Hearing Loss, Autoimmune hemolytic anemia, Autoimmune hypoparathyroidism, Autoimmune hypophysitis, Autoimmune Lymphoproliferative, Autoimmune Myocarditis, Autoimmune oophoritis, Autoimmune orchitis, Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal-Dystrophy, Autoimmune Syndrome Type II, Polyglandular, Behcet Syndrome, Celiac Disease, Chagas Disease, Cholangitis, Sclerosing, Chronic Inflammatory Demyelinating Polyneuropathy, Chronic lymphocytic thyroiditis, Churg-Strauss Syndrome, Colitis, Ulcerative, Crohn's disease, Cryoglobulinemia, Cushing Syndrome, Dermatitis Herpetiformis, Dermatomyositis, Diabetes Mellitus (Insulin-Dependent), Diffuse Cerebral Sclerosis of Schilder, Encephalomyelitis, Autoimmune, Experimental (EAE), Epidermolysis Bullosa Acquisita, Erythematosis, Felty's Syndrome, Glomerulonephritis (IGA), Glomerulonephritis Membranous, Goodpasture Syndrome, Graves' Disease, Guillain-Barre Syndrome, Hamman-Rich syndrome, Hepatitis Autoimmune, Hepatitis Chronic Active, Idiopathic thrombocytopenia, Inflammatory Bowel Diseases, Insulin resistance—type B, Lambert-Eaton Myasthenic Syndrome, Lens-induced uveitis, Lichen Sclerosus et Atrophicus, Lupus Erythematosus Discoid, Lupus Erythematosus Systemic, Lupus Hepatitis, Lupus Nephritis, Lymphopenia, Meniere's Disease, Mixed Connective Tissue Disease, Mooren's ulcer, Mucocutaneous Lymph Node Syndrome, Multiple Sclerosis, Myasthenia Gravis, Myelitis Transverse, Myocarditis, Narcolepsy, Neuritis Autoimmune Experimental, Neuromyelitis Optica, Oculovestibuloauditory syndrome, Ophthalmia Sympathetic, Opsoclonus-Myoclonus Syndrome, Pancreatitis, Pemphigoid Bullous, Pemphigus foliaceous, Pemphigus Vulgaris, Polyarteritis Nodosa, Polychondritis Relapsing, Polyendocrinopathies Autoimmune, Polymyalgia Rheumatica, Polyradiculoneuropathy, Primary biliary cirrhosis, Psoriasis, Purpura Thrombocytopenic Idiopathic, Raynauds, Reiter Disease, Rheumatic Fever, Rheumatoid Arthritis, Sarcoidosis, Scleroderma, Sjögren's Syndrome, Spondylitis Ankylosing, Stiff-Person Syndrome, Still's Disease Adult Onset, Takayasu's Arteritis, Temporal Arteritis, Thyrotoxicosis, Type B Insulin Resistance, Uveomeningo-encephalitic Syndrome, Wegener's Granulomatosis, and Vitiligo. 
     
     
         7 . The composition according to  claim 1 , wherein said composition is used for the treatment of Rheumatoid arthritis, Diabetes mellitus type I, Psoriasis, Sjögren's syndrome, Multiple Sclerosis, Crohn's disease, arteriosclerosis, Parkinson's disease, ALS (Amyotrophic lateral sclerosis) or dementia. 
     
     
         8 . The composition according to  claim 1 , wherein said composition is used in transplantations to inhibit immune rejection of organs, tissues, normal cells or gene therapeutically modified cells. 
     
     
         9 . A method of inducing IDO in a cell culture comprising the steps of;
 a) providing isolated cells in a suitable medium,   b) adding the composition according to  claim 1 ,   c) incubating said isolated cells with the composition and   d) obtaining a cell culture in which IDO is induced.   
     
     
         10 . A method of treating a mammal having an autoimmune disorder or disease or suffering from immune rejection of organs, tissues, normal cells or gene therapeutically modified cells, wherein the treatment induces IDO, comprising administering to a patient a therapeutically effective amount of the composition according to  claim 1 . 
     
     
         11 . A method of treating a mammal having an autoimmune disorder or disease or suffering from immune rejection of organs, tissues, normal cells or gene therapeutically modified cells, wherein the treatment induces IDO, comprising firstly a treatment ex vivo of cells derived from the treated mammal or from another mammal, with a therapeutically effective amount of the composition according to  claim 1  and in the presence of one or more antigens associated with a condition being treated, followed by the transfer of treated cells to the mammal being treated.