Use in brain degenerative diseases

Abstract

Disclosed is a new use for sphingosine-1-phosphate (S1P) receptor agonists in the treatment of progressive dementia or brain degenerative diseases.

1 . A pharmaceutical combination comprising a) a first agent which is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form, or FTY720-phosphate and b) a second agent, which is selected from an AMPA receptor agonist,
 wherein the AMPA receptor agonist is selected from quinoxaline-dione aminoalkylphosphonate; 7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine-8-carbonitrile; 4-(7-chloro-2-methyl-4H-3,10,10a-triaza-benzo[f]azulen-9-yl)-phenylamine; N,N-dimethyl-2-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenoxy]ethanamine; 7-[4-[[[[(4-carboxyphenyl)-amino]carbonyl]oxy]methyl]-1H-imidazol-1-yl]-3,4-dihydro-3-oxo-6-(trifluoromethyl)-2-quinoxalinecarboxylic acid; 2-[[[5-[4-[(dimethylamino)-sulfonyl]phenyl]-1,2,6,7,8,9-hexahydro-8-methyl-2-oxo-3H-pyrrolo[3,2-h]isoquinolin-3-ylidene]amino]oxy]-4-hydroxybutanoic acid monosodium salt; 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate; (R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzo-diazepine; 6-imidazol-1-yl-7-nitro-1,4-dihydro-quinoxaline-2,3-dione; 7-chloro-6-sulfamoyl-2-(1H)-quinolinone-3-phosphonic acid; 7-imidazol-1-yl-6-nitro-2,3-dioxo-3,4-dihydro-2H-quinoxalin-1-yl)-acetic acid; 4-(8-methyl-9H-1,3-dioxa-6,7-diaza-cyclohepta[f]inden-5-yl)-phenylamine; 7-morpholin-4-yl-2,3-dioxo-6-trifluoromethyl-3,4-dihydro-2H-quinoxalin-1-ylmethyl)-phosphonic acid; 3-(2-chloro-phenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one; 4-(4-amino-phenyl)-6-methoxy-1-methyl-1H-phthalazine-2-carboxylic acid propylamide; 8-(4-amino-phenyl)-5-methyl-5H-[1,3]dioxolo[4,5-g]phthalazine-6-carboxylic acid propylamide; (4-oxo-2-phosphono-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-9-yl)-acetic acid; and 6-[2-(1H-tetrazol-5-yl)-ethyl]-decahydro-isoquinoline-3-carboxylic acid.   
     
     
         2 . A pharmaceutical combination according to  claim 1  wherein the first agent is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form. 
     
     
         3 . A pharmaceutical combination according to  claim 1  wherein the first agent is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride. 
     
     
         4 . A pharmaceutical combination according to any preceding claims for use in reducing or inhibiting loss of cognitive abilities, treating progressive dementia or a disease selected from amyloidosis, Lewy Body diseases, Multi-Infarct dementia, Pick's disease and cerebral atherosclerosis.