Prevention and treatment of amyloidogenic disease

Abstract

The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.

1 - 30 . (canceled)  
     
     
         31 . A composition comprising an analog of a fragment of Aβ or an N-terminal segment thereof, wherein the fragment of Aβ or the N-terminal segment thereof contains an N-terminal truncation and/or a post-translational modification.  
     
     
         32 . The composition according to  claim 31 , wherein the N-terminal truncated fragment of Aβ or the N-terminal segment thereof starts at position 2 or 3 of Aβ and that the post-translational modification is a methylation.  
     
     
         33 . The composition according to  claim 31  or  32 , wherein the analog of the fragment of Aβ or the N-terminal segment thereof comprises an amino acid sequence selected from the group consisting of Aβ1-4, Aβ1-5, Aβ1-6, Aβ1-7, Aβ1-8, Aβ1-9, Aβ1-10, Aβ1-11, Aβ1-12, Aβ1-16, Aβ1-40, Aβ1-42, Aβ2-7, Aβ2-8, Aβ2-9, Aβ2-10, Aβ2-11, Aβ3-7, Aβ3-8, Aβ3-9, Aβ3-10, and Aβ3-11.  
     
     
         34 . A nucleic acid composition comprising a nucleic acid sequence capable of encoding the analog of the fragment of Aβ or the N-terminal segment thereof according to any of claims  31 - 33 .  
     
     
         35 . A method for the preparation of an antibody that specifically recognizes an N-terminal truncated and/or post-translationally modified analog of a fragment of Aβ or an N-terminal segment thereof, comprising the following steps: 
 (a) Immunizing an animal with the composition according to any of claims  31 - 33 , or with the nucleic acid composition according to  claim 34;     (b) Obtaining the antibodies generated in the immunization in step (a); and    (c) Screening the antibodies obtained in step (b) for their specific binding to an Aβ peptide, the peptide being an N-terminal truncated and/or post-translationally modified analog of a fragment of Aβ or an N-terminal segment thereof.    
     
     
         36 . An antibody obtainable by the method according to  claim 35 .  
     
     
         37 . A vaccine composition or a therapeutic composition comprising a composition according to any of claims  31 - 33 , an antibody according to  claim 36 , or a nucleic acid composition according to  claim 34 .  
     
     
         38 . A composition according to any of claims  31 - 33 , an antibody according to  claim 36 , or a nucleic acid composition according to  claim 34  for use as a prophylactic vaccine for the prevention of a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease.  
     
     
         39 . A composition according to any of claims  31 - 33 , an antibody according to  claim 36 , or a nucleic acid composition according to  claim 34  for use as a therapeutic for the treatment of a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease.  
     
     
         40 . Use of a composition according to any of claims  31 - 33 , an antibody according to  claim 36 , or a nucleic acid composition according to  claim 34  for the manufacture of a prophylactic for the prevention of a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease.  
     
     
         41 . Use of a composition according to any of claims  31 - 33 , an antibody according to  claim 36 , or a nucleic acid composition according to  claim 34  for the manufacture of a therapeutic for the treatment of a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease.  
     
     
         42 . A method for the prevention and/or treatment, in a mammal, of a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease, the method comprising administering to the mammal a vaccine composition or a therapeutic composition according to  claim 37 .  
     
     
         43 . A diagnostic or theranostic kit comprising a composition according to any of claims  31 - 33 , or an antibody according to  claim 36 .  
     
     
         44 . A composition according to any of claims  31 - 33  for use as a diagnostic or theranostic for the measurement of the immune response induced in a mammal by administering to the mammal a vaccine composition or a therapeutic composition according to  claim 37 .  
     
     
         45 . Use of a composition according to any of claims  31 - 33  for the manufacture of a diagnostic or theranostic kit for the measurement of the immune response induced in a mammal by administering to the mammal a vaccine composition or a therapeutic composition according to  claim 37 .  
     
     
         46 . A method for the measurement, in a mammal, of the immune response induced by administering to the mammal a vaccine composition or a therapeutic composition according to  claim 37 , the method comprising the following steps: 
 (a) Determining, in a sample obtained from the mammal, the amount of antibody specific for an N-terminal truncated and/or post-translationally modified analog of a fragment of Aβ or an N-terminal segment thereof according to any of claims  31 - 33 ;    (b) Comparing the amount determined in step (a) with the amount of antibody specific for the N-terminal truncated and/or post-translationally modified analog of a fragment of Aβ or an N-terminal segment thereof present in the mammal before administration of the vaccine or therapeutic composition according to  claim 37;     (c) Concluding, from the comparison in step (b), whether the mammal is responding to the administration of the vaccine or therapeutic composition according to  claim 37 , an increased amount of antibody specific for the N-terminal truncated and/or post-translationally modified analog of a fragment of Aβ or an N-terminal segment thereof being an indication that the mammal is responding to the administration of the vaccine or therapeutic composition according to  claim 37 .    
     
     
         47 . An antibody according to  claim 36  for use as a diagnostic or theranostic for determining, in a mammal, the susceptibility to a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease, or for determining, in a mammal, the risk of developing a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease.  
     
     
         48 . Use of an antibody according to  claim 36  for the manufacture of a diagnostic or theranostic kit for determining, in a mammal, the susceptibility to a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease, or for determining, in a mammal, the risk of developing a disease associated with β-amyloid formation and/or aggregation such as Alzheimer's disease.