Method for the treatment of apolipoprotein E related diseases

Abstract

Methods for treating diseases associated with toxicity of Apolipoprotein E (“apoE”). Specifically, the present invention relates to new methods for treating a mammal having a condition associated with toxicity of apolipoprotein E cleavage fragments containing residues 130-169, comprising administering to said mammal a pharmacologically effective amount of compound or a pharmaceutically acceptable sale, derivative or fragment thereof to interfere with the receptor-binding site associated with residues 130-169 of the apolipoprotein E molecule in said mammal.

What is claimed is:  
     
         1 . A method of preventing apolipoprotein E toxicity to a cell comprising treating said cell with a compound capable of inhibiting apolipoprotein E toxicity.  
     
     
         2 . The method of  claim 1 , wherein the compound is selected from the group consisting of polyvinyl sulfate, pentosan polysulfate, dextran sulfate, heparan sulfate and mixtures thereof.  
     
     
         3 . The method of  claim 1 , wherein the compound further comprises napthalenesulfonic acid covalently bonded to a phenyl or naphthyl group.  
     
     
         4 . The method of  claim 2 , wherein the napthalenesulfonic acid is covalently bonded to a phenyl or naphthyl group through a diazo or amide bond.  
     
     
         5 . The method of  claim 1 , wherein the compound is selected from the group consisting of ponceau S, Evan's blue, suramin sodium, direct blue 15, calconcarboxylic acid, amaranth, trypan blue, congo red, benzopurpurin 4b, Chicago sky blue 6b, sulfonazo III and mixtures thereof.  
     
     
         6 . The method of  claim 1 , wherein the compound further comprises a triphenylmethane core modified with at least one sulfate or carboxylate group.  
     
     
         7 . The method of  claim 1 , wherein the compound further comprises a triphenylmethane core modified with at least one benzoic acid or benzenesulfonic acid substituent.  
     
     
         8 . The method of  claim 7 , wherein the benzoic acid or benzenesulfonic acid substituents are covalently bound to the phenyl groups of the triphenylmethane through a nitrogen bond.  
     
     
         9 . The method of  claim 1 , wherein the compounds are selected from the group consisting of aurintricarboxylic acid, aniline blue, methyl blue, light green SF yellowish, Coomassie brilliant blue G-250, Coomassie brilliant blue R-250, and mixtures thereof.  
     
     
         10 . The method of  claim 1 , wherein the compound further comprises a tetrabromophenolsulfonphthalein.  
     
     
         11 . The method of  claim 1 , wherein the compound is selected from the group consisting of bromophenol blue, bromocresol green and mixtures thereof.  
     
     
         12 . The method of  claim 1 , wherein the compound is selected from the group consisting of cibacron blue, thiazol yellow G, sulfobromophthalein, biebrich scarlet and mixtures thereof.  
     
     
         13 . The method of  claim 1 , wherein inhibiting apolipoprotein E toxicity comprises inhibiting binding of apolipoprotein E or fragments of apolipoprotein E to a cell.  
     
     
         14 . The method of  claim 1 , wherein the fragments of apolipoprotein E comprise residues 141-147 of apolipoprotein E.  
     
     
         15 . The method of  claim 1 , wherein inhibiting apolipoprotein E toxicity comprises inhibiting production of a peptide fragment of apolipoprotein E comprising residues 141-147 of apolipoprotein E.  
     
     
         16 . A method of treating conditions associated with apolipoprotein E toxicity, comprising administering a composition comprising a pharmacologically effective amount of a compound that inhibits apolipoprotein E toxicity.  
     
     
         17 . The method of  claim 16 , wherein the compound is selected from the group consisting of polyvinyl sulfate, pentosan polysulfate, dextran sulfate, heparan sulfate and mixtures thereof.  
     
     
         18 . The method of  claim 16 , wherein the compound further comprises napthalenesulfonic acid covalently bonded to a phenyl or naphthyl group.  
     
     
         19 . The method of  claim 18 , wherein the napthalenesulfonic acid is covalently bonded to a phenyl or naphthyl group through a diazo or amide bond.  
     
     
         20 . The method of  claim 16 , wherein the compound is selected from the group consisting of ponceau S, Evan's blue, suramin sulfate, direct blue 15, calconcarboxylic acid, amaranth, trypan blue, congo red, benzopurpurin 4b, Chicago sky blue 6b, sulfonazo III and mixtures thereof.  
     
     
         21 . The method of  claim 16 , wherein the compound further comprises a triphenylmethane core modified with at least one sulfate or carboxylate group.  
     
     
         22 . The method of  claim 16 , wherein the compound further comprises a triphenylmethane core modified with at least one benzoic acid or benzenesulfonic acid substituent.  
     
     
         23 . The method of  claim 22 , wherein the benzoic acid or benzenesulfonic acid substituents are covalently bound to the phenyl groups of the triphenylmethane through a nitrogen bond.  
     
     
         24 . The method of  claim 16 , wherein the compounds are selected from the group consisting of aurintricarboxylic acid, aniline blue, methyl blue, light green SF yellowish, Coomassie brilliant blue G-250, Coomassie brilliant blue R-250, and mixtures thereof.  
     
     
         25 . The method of  claim 16 , wherein the compound further comprises a tetrabromophenolsulfonphthalein.  
     
     
         26 . The method of  claim 16 , wherein the compound is selected from the group consisting of bromophenol blue, bromocresol green and mixtures thereof.  
     
     
         27 . The method of  claim 16 , wherein the compound is selected from the group consisting of cibacron blue, thiazol yellow G, sulfobromophthalein, biebrich scarlet and mixtures thereof.  
     
     
         28 . The method of  claim 16 , wherein inhibiting apolipoprotein E toxicity comprises inhibiting binding of apolipoprotein E or fragments of apolipoprotein E to a cell.  
     
     
         29 . The method of  claim 28 , wherein the fragments of apolipoprotein E comprise residues 141-147 of apolipoprotein E.  
     
     
         30 . The method of  claim 16 , wherein inhibiting apolipoprotein E toxicity comprises inhibiting production of a peptide fragment of apolipoprotein E comprising residues 141-147 of apolipoprotein E.  
     
     
         31 . The method of  claim 16 , wherein the condition is Alzheimer's-type senile dementia.  
     
     
         32 . The method of  claim 16 , wherein the condition is a condition associated with cerebral amyloidosis.  
     
     
         33 . The method of  claim 16 , wherein the condition is hyperlipidemia.  
     
     
         34 . The method of  claim 16 , wherein the condition is selected from the group consisting of coronary heart disease, atherosclerosis, head injury, ischemic stroke, intracerebral hemorrhage, normal pressure hydrocephalus, HIV-associated dementia and HIV-associated peripheral neuropathy.