Method of providing patient specific immune response in amyloidoses and protein aggregation disorders

Abstract

A treatment of Alzheimer's disease and other disorders involving protein misfolding or aggregation is provided by enhancing or sustaining an antibody response against predominantly directed against pathological protein aggregates or neo-epitopes present on pathogenic forms of said protein or protein complex. Furthermore, therapeutic methods are described, wherein ex vivo stimulated antigen-selected peripheral blood lymphocytes are regrafted into the cognate donor.

1 - 47 . (canceled) 
     
     
         48 . A method of treating Alzheimer's Disease pathology, which method comprises:
 selecting a subject who has Alzheimer's Disease pathology; and   administering, to the selected subject an oligonucleotide or modified oligonucleotide containing at least one unmethylated B-class CpG dinucleotide motif at a dosage in a range of 0.2 mg to 20 mg per kilogram body weight of the selected subject, wherein said administering is effective to stimulate production of endogenously primed autoantibodies without co-administration of exogenous immunogens, said autoantibodies having binding specificity for one or more pathological neo-epitopes of amyloid beta or a beta-amyloid-associated protein, without stimulating production of autoantibodies having binding specificity for non-pathological epitopes of amyloid beta or a beta-amyloid-associated protein in the subject, thereby treating Alzheimer's Disease pathology.   
     
     
         49 - 50 . (canceled) 
     
     
         51 . The method of  claim 48 , wherein the oligonucleotide is formulated as a pharmaceutical composition, optionally together with a pharmaceutically acceptable carrier. 
     
     
         52 . The method of  claim 51 , wherein said pharmaceutical composition does not include an antigen comprising said pathological protein aggregate or neo-epitope consisting of amyloid beta and beta-amyloid-associated proteins. 
     
     
         53 . The method of  claim 48 , wherein the oligonucleotide is designed to be administered at a subclinical stage of the disorder. 
     
     
         54 . The method of  claim 51 , wherein said pharmaceutical composition comprises at least one non-nucleic acid adjuvant capable of creating a depo effect. 
     
     
         55 . The method of  claim 54 , wherein the adjuvant is selected from the group consisting of alum, emulsion based formulations, mineral oil, non-mineral oil, water-in-oil emulsions, water-in-oil-in-water emulsions and the Seppic ISA series of Montanide adjuvants. 
     
     
         56 . The method of  claim 54 , wherein the adjuvant comprises an immune stimulating adjuvant. 
     
     
         57 . The method of  claim 54 , wherein the adjuvant comprises vitamin A. 
     
     
         58 . The method of  claim 54 , wherein the adjuvant comprises a compound selected from the group consisting of saponins, PCPP polymer, derivatives of lipopolysaccharides, Monophosphoryl A (MPL), muramyldipeptide (MDP), threonylmuramyl dipeptide (t-MDP),  Leishmania  elongation factor, and glatiramer acetate. 
     
     
         59 . The method of  claim 54 , wherein the adjuvant that creates a depo effect and stimulates the immune system is selected from the group consisting of Immune Stimulating Complexes (ISCOMS), Adjuvant System 2 (AS2), Adjuvant System 4 (AS4), non-ionic block copolymers and Syntex adjuvant formulation (SAF). 
     
     
         60 . The method of  claim 48 , wherein said administering is performed intravenously, intramuscularly, subcutaneously, intraperitoneally, intranasally, parenterally or as an aerosol. 
     
     
         61 . An oligonucleotide or modified oligonucleotide containing at least one unmethylated B-class CpG dinucleotide motif for the treatment of a subject who has Alzheimer's Disease pathology. 
     
     
         62 . The oligonucleotide or modified oligonucleotide of  claim 61 , wherein the modified oligonucleotide is phosphorothioate-modified. 
     
     
         63 . A kit for characterizing plaque structures comprising:
 an oligonucleotide or modified oligonucleotide containing at least one unmethylated B-class CpG dinucleotide motif;   reagents for detection of pathological protein aggregate or neo-epitope binding; and   instructions for use.   
     
     
         64 . The kit of  claim 63 , wherein the oligonucleotide or modified oligonucleotide is phosphorothioate-modified.