Methods and compositions for diseases associated with amyloidosis

Abstract

The present invention generally relates to the detection, treatment or prevention of disease states. Specifically, the present invention relates to the detection, treatment or prevention of amyloidosis or amyloid-associated diseases. The present invention further comprises methods and compositions comprising therapeutic vaccines, antisera and molecular constructs, comprising expression vectors and fusion proteins encoded therein.

1 . A tetra-palmitoylated beta-amyloid peptide having an N terminus and a C terminus. 
     
     
         2 . The tetra-palmitoylated beta-amyloid peptide of  claim 1 , wherein at least one of the palmitoyl moieties is on a lysine residue forming a palmitoylated lysine residue. 
     
     
         3 . The tetra-palmitoylated beta-amyloid peptide of  claim 2 , wherein the palmitoylated lysine residue is at the C-terminus of the tetra-palmitoylated beta-amyloid peptide. 
     
     
         4 . The tetra-palmitoylated beta-amyloid peptide of  claim 3 , having a second palmitoylated lysine residue at the C-terminus of tetra-palmitoylated the beta-amyloid peptide. 
     
     
         5 . The tetra-palmitoylated beta-amyloid peptide of  claim 2 , wherein the palmitoylated lysine residue is at the N-terminus of the tetra-palmitoylated beta-amyloid peptide. 
     
     
         6 . The tetra-palmitoylated beta-amyloid peptide of  claim 4 , further comprising a second palmitoylated lysine residue at the N-terminus of the beta-amyloid peptide. 
     
     
         7 . The tetra-palmitoylated beta-amyloid peptide of  claim 2 , wherein each of the four palmitoyl moieties are on lysine residue forming four palmitoylated lysine residues such that the tetra-palmitoylated beta-amyloid peptide has a palmitoylated lysine residue is at the C terminus and a palmitoylated lysine residue at the N-terminus. 
     
     
         8 . The tetra-palmitoylated beta-amyloid peptide of  claim 7 , having two palmitoylated lysine residues at the C-terminus and two palmitoylated lysine residues at the N-terminus. 
     
     
         9 . The tetra-palmitoylated beta-amyloid peptide of any of  claims 1 - 8 , wherein the beta-amyloid portion of the tetra-palmitoylated beta-amyloid peptide is the beta-amyloid 1-16 peptide. 
     
     
         10 . A composition comprising the tetra-palmitoylated beta-amyloid peptide of any one of  claims 1  through  8 , wherein the tetra-palmitoylated beta amyloid peptide is anchored in a liposomal bilayer. 
     
     
         11 . The composition of  claim 10  wherein the liposomal bilayer is a liposome. 
     
     
         12 . A pharmaceutical composition comprising the tetra-palmitoylated beta-amyloid peptide of any of  claims 1 - 8  and a carrier. 
     
     
         13 . A pharmaceutical composition comprising the composition of  claim 10  and a carrier. 
     
     
         14 . A method for treating an amyloid-associated disease in a subject, comprising administering to the subject an effective amount of the tetra-palmitoylated beta-amyloid peptide of any of  claims 1 - 8 . 
     
     
         15 . The method of  claim 14 , wherein the amyloid-associated disease is Alzheimer's disease. 
     
     
         16 . The method of  claim 14 , wherein the amyloid-associated disease comprises Type 2 diabetes mellitus, amyloid A (reactive), secondary amyloidosis, familial mediterranean fever, familial amyloid nephropathy with urticaria and deafness, Muckle-wells Syndrome, myeloma, macroglobulinemia associated Muckle-Wells Syndrome, chronic hemodialysis, ATTR, familial amyloid polyneuropathy, familial amyloid cardiomyopathy, isolated cardiac amyloid, systemic senile amyloidosises, AIAPP, amylin insulinoma, atrial naturetic factor, procalcitonin, gelsolin, cystatin C, AApo-A-I, AApo-A-II, fibrinogen-associated amyloid, scrapie, Creutzfeld Jacob disease, Gertsmann-Straussler-Scheinker syndrome, bovine spongiform encephalitis, or persons who are homozygous for the apolipoprotein E4 allele. 
     
     
         17 . A composition comprising the tetra-palmitoylated beta-amyloid peptide of  claim 9 , wherein the tetra-palmitoylated beta amyloid peptide is anchored in a liposomal bilayer. 
     
     
         18 . The composition of  claim 17  wherein the liposomal bilayer is a liposome. 
     
     
         19 . A pharmaceutical composition comprising the tetra-palmitoylated beta-amyloid peptide of  claim 9  and a carrier. 
     
     
         20 . A pharmaceutical composition comprising the composition of  claim 17  and a carrier. 
     
     
         21 . A method for treating an amyloid-associated disease in a subject, comprising administering to the subject an effective amount of the tetra-palmitoylated beta-amyloid peptide of  claim 9 . 
     
     
         22 . The method of  claim 21 , wherein the amyloid-associated disease is Alzheimer's disease. 
     
     
         23 . The method of  claim 21 , wherein the amyloid-associated disease comprises Type 2 diabetes mellitus, amyloid A (reactive), secondary amyloidosis, familial mediterranean fever, familial amyloid nephropathy with urticaria and deafness, Muckle-wells Syndrome, myeloma, macroglobulinemia associated Muckle-Wells Syndrome, chronic hemodialysis, ATTR, familial amyloid polyneuropathy, familial amyloid cardiomyopathy, isolated cardiac amyloid, systemic senile amyloidosises, AIAPP, amylin insulinoma, atrial naturetic factor, procalcitonin, gelsolin, cystatin C, AApo-A-I, AApo-A-II, fibrinogen-associated amyloid, scrapie, Creutzfeld Jacob disease, Gertsmann-Straussler-Scheinker syndrome, bovine spongiform encephalitis, or persons who are homozygous for the apolipoprotein E4 allele.