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 . An antibody molecule capable of specifically recognizing two regions of the A4 peptide/Aβ4, wherein the first region comprises the amino acid sequence AEFRHDSGY or a fragment thereof and wherein the second region comprises the amino acid sequence YEVHHQKLVFFAEDVG or a fragment thereof.  
     
     
         2 . The antibody molecule of  claim 1 , wherein said antibody molecule recognizes at least two contiguous amino acids within the two regions of β-A4.  
     
     
         3 . The antibody molecule of  claim 1  or  2 , wherein said antibody molecule recognizes in the first region an amino acid sequence comprising: AEFRHD, or EFRHDSG, EFRHD and in the second region an amino acid sequence comprising: VFFA, or QKLFFAEDV.  
     
     
         4 . The antibody molecule of any one of  claims 1  to  3 , wherein said antibody molecule is a full antibody (immunoglobulin), a F (ab)-fragment, a F (ab) 2-fragment, a single-chain antibody, a chimeric antibody, a CDR-grafted antibody, or a recombinant antibody.  
     
     
         5 . The antibody molecule of any one of  claims 1  to  4 , wherein said at least two regions of β-A4 form a conformational epitope.  
     
     
         6 . A nucleic acid molecule encoding an antibody molecule of any one of  claims 1  to  5 .  
     
     
         7 . A vector comprising the nucleic acid molecule of  claim 6 .  
     
     
         8 . A host cell comprising the vector of  claim 7 .  
     
     
         9 . A method for the preparation of an antibody molecule of any one of  claims 1  to  5  comprising culturing the host cell of  claim 8  under conditions that allow synthesis of said antibody molecule and recovering said antibody molecule from said culture.  
     
     
         10 . A composition comprising an antibody molecule of any one of  claims 1  to  5  or an antibody molecule produced by the method of  claim 9 .  
     
     
         11 . The composition of  claim 10 , which is a pharmaceutical or a diagnostic composition.  
     
     
         12 . Use of an antibody molecule of any one of  claims 1  to  5  or an antibody molecule produced by the method of  claim 9 , of a nucleic acid molecule of  claim 6 , of a vector of  claim 7  or a host of  claim 8  for the preparation of a pharmaceutical composition for the prevention and/or treatment of an amyloidogenic disease and/or amyloid-plaque formation.  
     
     
         13 . Use of an antibody molecule of any one of  claims 1  to  5  or an antibody molecule produced by the method of  claim 9  for the preparation of a diagnostic composition for the detection of an amyloidogenic disease and/or amyloid-plaque formation.  
     
     
         14 . Use of an antibody molecule of any one of  claims 1  to  5  or an antibody molecule produced by the method of  claim 9  for the preparation of a pharmaceutical composition for the clearing of β-amyloid plaques.  
     
     
         15 . Use of an antibody molecule of any one of  claims 1  to  5  or an antibody molecule produced by the method of  claim 9  for the preparation of a pharmaceutical composition for passive immunization against-amyloid plaque formation.  
     
     
         16 . The use of claims  12  or  13 , wherein said disease is dementia, Alzheimer's disease, Down's syndrome, amyloidosis, or neuronal disorders related to aging.  
     
     
         17 . Kit comprising an antibody molecule of any one of  claims 1  to  5 , a nucleic acid molecule of  claim 6 , a vector of  claim 7  or a host cell of  claim 8.