Prevention and treatment of amyloidogenic disease
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.