AChE antisense oligonucleotide as an anti-inflammatory agent

Abstract

Disclosed is a novel use for AChE antisense oligonucleotides as anti-inflammatory agents, wherein said oligonucleotides are preferably as denoted by SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:7. Methods of treatment of inflammatory conditions, as well as fever, and particularly inflammation-associated neuropathies such as Guillain-Barré Syndrome, are described.

1 . A method of treatment of a condition triggering an inflammatory response in a mammalian subject, comprising administering to the subject a therapeutically effective amount of an inhibitor of AChE expression or a pharmaceutical composition comprising the same. 
     
     
         2 . A method for the treatment and/or prevention of inflammation in the joints, central nervous system, gastrointestinal tract, endocardium, pericardium, lung, eyes, skin and urogenital system of a mammalian subject, comprising administering to the subject a therapeutically effective amount of an inhibitor of AChE expression or a pharmaceutical composition comprising the same. 
     
     
         3 . A method for suppressing the release of a pro-inflammatory cytokine, comprising administering a therapeutically effective amount of an inhibitor of AChE expression or a pharmaceutical composition comprising the same, to a subject. 
     
     
         4 . A method for treating fever, comprising administering a therapeutically effective amount of an inhibitor of AChE expression or a pharmaceutical composition comprising the same, to a subject. 
     
     
         5 . A method for the treatment of an inflammation-associated neuropathy, comprising administering a therapeutically effective amount of an inhibitor of AChE expression or a pharmaceutical composition comprising the same, to a subject. 
     
     
         6 . The method of  claim 5 , wherein said inflammation-associated neuropathy is Guillain-Barré Syndrome. 
     
     
         7 . The method of  claim 1 , wherein said inhibitor of AChE expression is any one of an AChE-specific ribozyme, an RNA sequence used for RNA interference of the AChE gene, or an antisense oligonucleotide directed against AChE. 
     
     
         8 . The method of  claim 1 , wherein said inhibitor of AChE expression is a nuclease resistant antisense nucleotide directed against AChE or a functional analog, derivative, or fragment thereof. 
     
     
         9 . The method of  claim 7 , wherein said inhibitor of AChE expression is an antisense oligonucleotide directed against AChE, having the sequence as denoted by any one of SEQ ID No:1, SEQ ID No:2 or SEQ ID No:7, or a functional analog, derivative, or fragment thereof. 
     
     
         10 . The method of  claim 7 , wherein said inhibitor of AChE expression is an antisense oligonucleotide directed against AChE, having the sequence as denoted by SEQ. ID. NO:1, or a functional analog, derivative, or fragment thereof. 
     
     
         11 . The method of  claim 3 , wherein said pro-inflammatory cytokine is selected from the group consisting of IL-1β, TNFα, IL-6, IL-8, IL-12, and IL-18. 
     
     
         12 . The method of  claim 3 , wherein said pro-inflammatory cytokine release is triggered by one of stress, bacterial infection, drugs, irradiation, exposure to AChE inhibitors, stroke, auto-immune diseases, multiple chemical sensitivity, and any cumulative age-dependent damages. 
     
     
         13 . The method of  claim 1 , wherein said mammalian subject is a human, and said inhibitor of AChE expression is an antisense oligonucleotide directed against AChE, as denoted by the sequence selected from SEQ. ID. NO:1 and SEQ. ID. NO:7, or a functional analog, derivative, or fragment thereof. 
     
     
         14 . The method of  claim 10 , wherein said antisense oligonucleotide or composition comprising the same is for daily use by the subject, and said therapeutically effective amount is a dosage of active ingredient between about 0.001 μg/g and about 50 μg/g. 
     
     
         15 . The method of  claim 14 , wherein said dosage of active ingredient is between about 0.01 and about 5.0 μg/g. 
     
     
         16 . The method of  claim 15 , wherein said dosage of active ingredient is between about 0.15 and about 0.50 μg/g. 
     
     
         17 . The method of  claim 1 , wherein said conditions are selected from any one of stress, bacterial infection, drugs, irradiation, exposure to AChE inhibitors, stroke, auto-immune diseases, multiple chemical sensitivity and any cumulative age-dependent damages.