Compounds and methods for the treatment of inflammatory diseases of the CNS

Abstract

Inflammatory diseases in the CNS can be treated or alleviated by the administration of an oligonucleotide in an amount sufficient to reduce the influx of mononuclear cells to the central nervous system by down-regulating the expression of at least one cell surface marker. For example multiple sclerosis can be treated or at least alleviated, by the administration of an oligonucleotide in a dose effective to inhibit or reduce the influx of mononuclear and/or autoaggressive cells to the central nervous system. The oligonucleotide can be used alone, or in combination with other treatment strategies.

1 . A method for the treatment, and/or alleviation of multiple sclerosis, comprising administering an oligonucleotide to a patient in need thereof in an amount effective to inhibit or reduce the influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker, wherein the oligonucleotide is an isolated and substantially purified oligonucleotide selected from the group consisting of SEQ ID NO: 9 (IDX0150), and SEQ ID NO: 10 (IDX0980). 
     
     
         2 . The method according to  claim 1 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         3 . The method according to  claim 1 , wherein the oligonucleotide is SEQ ID NO: 10 (IDX0980). 
     
     
         4 . The method according to  claim 1 , wherein the cell surface marker is at least one of CD49d, CXCR3 (CD183), CCR2 (CD192), and CCR5 (CD195). 
     
     
         5 . The method of  claim 4 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         6 . The method of  claim 4 , wherein the cell surface marker is CD49d and the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         7 . The method according to  claim 1 , wherein the route of administration is chosen from mucosal, subcutaneous, intramuscular, intravenous and intraperitoneal administration. 
     
     
         8 . The method according to  claim 7 , wherein the mucosal administration is chosen from nasal, oral, gastric, ocular, rectal, urogenital and vaginal administration. 
     
     
         9 . The method according to  claim 7 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         10 . The method according to  claim 8 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         11 . A method for the treatment, and/or alleviation of multiple sclerosis, wherein an oligonucleotide is administered to a patient in need thereof in an amount effective to inhibit or reduce the influx of mononuclear and/or autoaggressive cells to the central nervous system by reducing the production of VEGF, wherein the oligonucleotide is an isolated and substantially purified oligonucleotide selected from the group consisting of SEQ ID NO: 9 (IDX0150), and SEQ ID NO: 10 (IDX0980). 
     
     
         12 . The method according to  claim 11 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         13 . The method according to  claim 11 , wherein the oligonucleotide is SEQ ID NO: 10 (IDX0980). 
     
     
         14 . The method according to  claim 11 , wherein the route of administration is chosen from mucosal, subcutaneous, intramuscular, intravenous and intraperitoneal administration. 
     
     
         15 . The method according to  claim 14 , wherein the mucosal administration is chosen from nasal, oral, gastric, ocular, rectal, urogenital and vaginal administration. 
     
     
         16 . The method according to  claim 14 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150). 
     
     
         17 . The method according to  claim 15 , wherein the oligonucleotide is SEQ ID NO: 9 (IDX0150).