Use of methylation inhibitors for the treatment of autoimmune diseases

A method for treating-an- rheumatoid arthritis in a patient comprising:

• administering to the patient in need thereof, a combination of a pharmaceutically effective amount of a DNA methylation inhibitor wherein the DNA methylation inhibitor is selected from the group consisting of:
• P1 4-Amino-1-(β-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one (azacitidine or AzaC), 2′-Deoxy-5-azacytidine, 4-Amino-1-(2-deoxy-β-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one (5-aza-2′-deoxycytidine)(dAzaC), N-[4-[(2-amino-6-methyl-4-pyrimidinyl)amino]phenyl]-4-(4-quinolinylamino)-benzamide (SGI-1027), epigallocatechin-3-gallate (EGCG), N-phthaloyl-1-tryptophan (RG108), caffeic acid, chlorogenic acid, hydralazine hydrochloride, procainamide hydrochloride, procaine hydrochloride, and 2-Amino-6-[(4-bromo-2-thienyl)methoxy]-9H-purine) (lomeguatrib);
• and
• a pharmaceutically effective amount of a histone methylation inhibitor wherein the histone methylation inhibitor is selected from the group consisting of:
• 1-cyclopentyl-N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-6-[4-(4-morpholinylmethyl)phenyl]-1H-indazole-4-carboxamide (EPZ005687), 7-[5-Deoxy-5-[[3-[[[[4-(1,1-dimethylethyl)phenyl]amino]carbonyl]amino]propyl](1-methylethyl)amino]-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (EPZ004777), N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-methyl-1-[(1S)-1-methylpropyl]-6-[6-(1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide (GSK126), N4-(1-benzylpiperidin-4-yl)-N2-(3-(dimethylamino)propyl)-6,7-dimethoxyquinazoline-2,4-diamine (E11), 2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-6,7-dimethoxy-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine trihydrochloride (BIX01294), N-[(1,2-dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide (GSK343), N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide (GSK503), N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-5-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-4-methyl-4′-(4-morpholinylmethyl)-[1,1′-biphenyl]-3-carboxamide (EPZ6438), chaetocin, and
• ((R)—N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205);
• and
• reversing arthritis specific epigenetic changes.