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 - 50 . (canceled) 
     
     
         51 . A method of treating Alzheimer's Disease pathology in a subject, which method comprises:
 administering, to the subject twice weekly for at least 3 months, 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 treat Alzheimer's Disease pathology.   
     
     
         52 . The method according to  claim 51 , wherein said administering is carried out for 3 to 5 months. 
     
     
         53 . The method according to  claim 51 , wherein said administering is carried out for 3 months. 
     
     
         54 . The method according to  claim 51 , wherein said administering is carried out for 4 months. 
     
     
         55 . The method according to  claim 51 , wherein the administering is carried out for 5 months. 
     
     
         56 . The method according to  claim 51 , wherein the oligonucleotide is formulated as a pharmaceutical composition, optionally together with a pharmaceutically acceptable carrier. 
     
     
         57 . The method of  claim 51 , wherein the oligonucleotide is administered at a subclinical stage of the disease. 
     
     
         58 . The method of  claim 51 , wherein the oligonucleotide is formulated as a pharmaceutical composition, optionally together with a pharmaceutically acceptable carrier. 
     
     
         59 . The method of  claim 58 , wherein said pharmaceutical composition comprises at least one non-nucleic acid adjuvant capable of creating a depo effect. 
     
     
         60 . The method of  claim 59 , 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. 
     
     
         61 . The method of  claim 59 , wherein the adjuvant comprises an immune stimulating adjuvant. 
     
     
         62 . The method of  claim 59 , wherein the adjuvant comprises vitamin A. 
     
     
         63 . The method of  claim 59 , 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. 
     
     
         64 . The method of  claim 59 , 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). 
     
     
         65 . The method of  claim 51 , wherein said administering is performed intravenously, intramuscularly, subcutaneously, intraperitoneally, intranasally, parenterally, or as an aerosol. 
     
     
         66 . The method of  claim 51 , wherein the oligonucleotide or modified oligonucleotide contains at least two unmethylated B-class CpG dinucleotide motifs. 
     
     
         67 . The method of  claim 51 , wherein the oligonucleotide or modified oligonucleotide contains two unmethylated B-class CpG dinucleotide motifs. 
     
     
         68 . The method of  claim 51 , wherein said administering is carried out without co-administration of exogenous immunogens. 
     
     
         69 . The method of  claim 51 , wherein the subject has a mutation in the beta-amyloid precursor protein (APP) gene. 
     
     
         70 . The method of  claim 51 , wherein the subject has familial Alzheimer's Disease. 
     
     
         71 . The method of  claim 51 , wherein said administering is effective to induce an autoantibody response. 
     
     
         72 . The method according to  claim 51 , wherein said administering is effective to reduce (i) total and compact Aβ plaque pathology, (ii) soluble brain Aβ40 and Aβ42, and/or (iii) insoluble brain Aβ40 and Aβ42 as compared to when said administering is not carried out, thereby treating Alzheimer's Disease pathology.