Immunological methods and compositions for the treatment of alzheimer's disease
OwnerPeter H. St. George-Hyslop, JoAnne McLaurininventors
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Abstract
The present invention relates to immunogenic compositions and peptides comprising residues 4-10 (FRHDSGY) of the amyloid peptide Abeta42. The invention further relates to antibodies that bind to the Abeta(4-10) antigenic determinant. The invention provides methods for treating Alzheimer's disease and for reducing the amyloid load in Alzheimers patients. The invention also relates to methods for designing small molecule inhibitors of amyloid deposition.
Claims19
A peptide represented by the formula
- (A)n--(Th)m--(B)o--Abeta(4-10)--(C)p
- wherein each of A, B and C are an amino acid residue or a sequence of amino acid residues;
- wherein n, o, and p are independently integers ranging from 0 to about 20;
- Th is independently a sequence of amino acid residues that comprises a helper T cell epitope or an immune enhancing analog or segment thereof;
- when o is equal to 0 then Th is directly connected to the B cell epitope through a peptide bond without any spacer residues;
- wherein m is an integer from 1 to about 5;
- and
- Abeta(4-10) is (SEQ ID NO:1), or an analog thereof containing a conservative amino acid substitution.
A peptide composition comprising a mixture of two or more peptides represented by the formula
- (A)n--(Th)m--(B)o--Abeta(4-10)--(C)p
- wherein each of A, B and C are an amino acid residue or a sequence of amino acid residues;
- wherein n, o, and p are independently integers ranging from 0 to about 20;
- Th is independently a sequence of amino acid residues that comprises a helper T cell epitope or an immune enhancing analog or segment thereof;
- when o is equal to 0 then Th is directly connected to the B cell epitope through a peptide bond without any spacer residues;
- wherein m is an integer from 1 to about 5;
- and
- Abeta(4-10) is (SEQ ID NO:1), or an analog thereof containing a conservative amino acid substitution.
An immunogenic composition for inducing the production of antibodies that specifically bind to an amyloid-beta peptide (SEQ ID NO:2) comprising:
- (a) an antigen, comprising a T-cell epitope that provides an effective amount of T-cell help and a B-cell epitope consisting of peptide Abeta(4-10) (SEQ ID NO:1);
- and
- (b) an adjuvant.
An isolated antibody or antigen binding fragment thereof capable of binding to peptide Abeta(4-10) (SEQ ID NO:1).
A method for treating an individual afflicted with Alzheimer's disease comprising administering to the individual an effective amount of an antibody composition which recognizes and binds to peptide Abeta(4-10) (SEQ ID NO:1).
A method for determining if a compound is an inhibitor of amyloid deposition and fibril formation comprising:
- (i) contacting the compound with the peptide Abeta(4-10) (SEQ ID NO:1);
- and
- (ii) detecting the binding of the compound with the peptide.
Dependencies are inferred from the claim text.