Monoclonal anti-alpha-synuclein antibodies for preventing tau aggregation
The invention relates to a novel use of monoclonal anti-alpha-synuclein antibodies. The antibodies can be used to prevent tau aggregation and thereby treating tauopathies such as Alzheimer's disease.
1. A method for treating Alzheimer's disease without Lewy body pathology in a patient comprising:
providing a monoclonal antibody, or an antigen-binding fragment thereof, that specifically binds alpha-synuclein to a patient having Alzheimer's disease without Lewy body pathology in an amount effective to inhibit aggregation of tau in the patient, wherein:
(i) the antibody, or antigen-binding fragment thereof, comprises:
a Heavy Chain CDR1 having the amino acid sequence of SEQ ID NO:1;
a Heavy Chain CDR2 having the amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:33, SEQ ID NO:34, or SEQ ID NO:35;
a Heavy Chain CDR3 having the amino acid sequence of SEQ ID NO:3;
a Light Chain CDR1 having the amino acid sequence of SEQ ID NO:4;
a Light Chain CDR2 having the amino acid sequence of SEQ ID NO:5; and
a Light Chain CDR3 having the amino acid sequence of SEQ ID NO:6; or
(ii) the antibody, or antigen-binding fragment thereof, comprises:
a Heavy Chain CDR1 having the amino acid sequence of SEQ ID NO:20;
a Heavy Chain CDR2 having the amino acid sequence of SEQ ID NO:21;
a Heavy Chain CDR3 having the amino acid sequence of SEQ ID NO:22;
a Light Chain CDR1 having the amino acid sequence of SEQ ID NO:23;
a Light Chain CDR2 having the amino acid sequence of SEQ ID NO:24; and
a Light Chain CDR3 having the amino acid sequence of SEQ ID NO:25.
2. The method of claim 1 , wherein the antibody binds aggregated soluble forms of alpha-synuclein.
3. The method of claim 1 , wherein the patient does not have Lewy body variant of Alzheimer's disease or combined Parkinson and Alzheimer's disease.
4. The method of claim 1 , wherein said antibody or antigen-binding fragment thereof binds to the C-terminal part of alpha-synuclein.
5. The method of claim 4 , wherein the antibody or antigen-binding fragment thereof binds to an epitope within the C-terminal amino acids 110-140 of human alpha-synuclein (SEQ ID NO 10).
6. The method of claim 4 , wherein said epitope is within amino acids 112-117, 112-115, 118-126, 126-138 or 136-140 of human alpha-synuclein (SEQ ID NO 10).
7. A pharmaceutical composition comprising the monoclonal antibody, or antigen-binding fragment thereof, according to claim 1 , and a pharmaceutical acceptable carrier.