Antibodies recognizing α-synuclein
The invention provides monoclonal antibody 5C1 and related antibodies. The 5C1 antibody binds to an epitope within residues 118-126 of α-synuclein. The antibodies of the invention are useful, for example, for treating and/or diagnosing disorders associated with α-synuclein, particularly accumulation of α-synuclein deposits. Such disorders include Lewy body diseases, such as Parkinson's disease, Diffuse Lewy Body Disease (DLBD), Lewy body variant of Alzheimer's disease (LBV), Combined Alzheimer's and Parkinson disease, pure autonomic failure and multiple system atrophy (MSA).
1. A method of treating, reducing risk, lessening severity or delaying onset of a Lewy body disease in a patient having or at risk of a Lewy body disease comprising administering to the patient an effective regime of an antibody comprising three light chain CDRs and three heavy chain CDRs of monoclonal antibody 5C1, wherein 5C1 is a mouse antibody characterized by a heavy chain variable region having an amino acid sequence comprising SEQ ID NO: 9 and light chain variable region having an amino acid sequence comprising SEQ ID NO: 24 and thereby treating, reducing risk, lessening severity or delaying onset of the disease.
2. The method of claim 1 , wherein the disease is Parkinson's disease.
3. The method of claim 1 , wherein the disease is multiple system atrophy (MSA) or Dementia with Lewy Bodies (DLB).
4. The method of claim 1 , wherein the method inhibits decline of cognitive function in the patient.
5. The method of claim 1 , wherein the method reduces neuritic and/or axonal alpha synuclein aggregates.
6. The method of claim 1 , wherein the method reduces neuritic dystrophy in the patient.
7. The method of claim 1 , wherein the method preserves synaptic and/or dendritic densities.
8. The method of claim 1 , where in the antibody comprises three heavy chain CDRs of SEQ ID NO: 9 as defined by Kabat and three light chain CDRs of SEQ ID NO: 24 as defined by Kabat.
9. The method of claim 1 , wherein the antibody has a human IgG1 Isotype.
10. The method of claim 1 , wherein the antibody comprises a mature heavy chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 17 and a mature light chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 31, wherein the antibody specifically binds to human alpha synuclein.
11. The method of claim 1 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.
12. The method of claim 11 , wherein the mature heavy chain variable region is fused to a heavy chain constant region having the sequence of SEQ ID NO: 38 and/or the mature light chain variable region is fused to a light chain constant region having the sequence of SEQ ID NO: 40.
13. The method of claim 11 , wherein the mature heavy chain variable region has an amino acid sequence comprising SEQ ID NO: 17 and the mature light chain variable region has an amino acid sequence comprising SEQ ID NO: 31.
14. A method of inhibiting synuclein aggregation or reducing Lewy bodies or synuclein aggregates in a patient having or at risk of a Lewy body disease, comprising administering to the patient an effective amount of an antibody comprising three light chain CDRs and three heavy chain CDRs of monoclonal antibody 5C1, wherein 5C1 is a mouse antibody characterized by a heavy chain variable region having an amino acid sequence comprising SEQ ID NO: 9 and light chain variable region having an amino acid sequence comprising SEQ ID NO: 24 and thereby inhibiting synuclein aggregation or reducing Lewy bodies or synuclein aggregates.
15. The method of claim 14 , wherein the disease is Parkinson's disease.
16. The method of claim 14 , wherein the disease is multiple system atrophy (MSA) or Dementia with Lewy Bodies (DLB).
17. The method of claim 14 , wherein the method inhibits decline of cognitive function in the patient.
18. The method of claim 14 , wherein the method reduces neuritic and/or axonal alpha synuclein aggregates.
19. The method of claim 14 , wherein the method reduces neuritic dystrophy in the patient.
20. The method of claim 14 , wherein the method preserves synaptic and/or dendritic densities.
21. The method of claim 14 , wherein the antibody comprises three heavy chain CDRs of SEQ ID NO: 9 as defined by Kabat and three light chain CDRs of SEQ ID NO: 24 as defined by Kabat.
22. The method of claim 14 , wherein the antibody has a human IgG1 isotype.
23. The method of claim 14 , wherein the antibody comprises a mature heavy chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 17 and a mature light chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 31, wherein the antibody specifically binds to human alpha synuclein.
24. The method of claim 14 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.
25. The method of claim 24 , wherein the mature heavy chain variable region is fused to a heavy chain constant region having the sequence of SEQ ID NO: 38 and/or the mature light chain variable region is fused to a light chain constant region having the sequence of SEQ ID NO: 40.
26. The method of claim 24 , wherein the mature heavy chain variable region has an amino acid sequence comprising SEQ ID NO: 17 and the mature light chain variable region has an amino acid sequence comprising SEQ ID NO: 31.