Prevention and treatment of synucleinopathic and amyloidogenic disease
The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.
1. A method of reducing the risk of, lessening the severity of, delaying the outset of or treating a disease characterized by Lewy bodies or alpha-synuclein aggregation in the brain, the method comprising
administering to a patient having or at risk of the disease an effective regime of a monoclonal antibody that competes with antibody 6H7 deposited as ATCC PTA-6910 for specific binding to alpha synuclein and specifically binds to an epitope within residues 1-10 of human alpha-synuclein, residues being numbered according to SEQ ID NO:1.
2. The method of claim 1 , wherein the antibody is a humanized antibody.
3. The method of claim 1 , wherein the antibody is a human antibody.
4. The method of claim 1 , wherein the antibody is an antibody of human IgG 1 isotype.
5. The method of claim 1 , wherein the antibody is administered with a pharmaceutical carrier as a pharmaceutical composition.
6. The method of claim 1 , wherein the antibody is administered at a dosage of 0.01-5 mg/kg.
7. The method of claim 1 , wherein the antibody is administered in multiple dosages over at least six months.
8. The method of claim 1 , wherein the antibody is administered as a sustained release composition.
9. The method of claim 1 , wherein the antibody is administered intraperitoneally, orally, subcutaneously, intracranially, intramuscularly, topically, intranasally or intravenously.
10. The method of claim 1 , wherein the antibody is 6H7 deposited as ATCC PTA-6910 or a humanized or chimeric version thereof.
11. A method of reducing the risk of, lessening the severity of, delaying the outset of or treating a disease characterized by Lewy bodies or alpha- synuclein aggregation in the brain, the method comprising
administering to a patient having or at risk of the disease an effective regime of a first monoclonal antibody that competes with antibody 6H7 deposited as ATCC PTA-6910 for specific binding to alpha synuclein and specifically binds to an epitope within residues 1-10 of human alpha-synuclein, residues being numbered according to SEQ ID NO:1 and administering a second antibody that that specifically binds to an epitope within residues 100-140 of human alpha-synuclein.
12. The method of claim 11 wherein the second antibody specifically binds to an epitope within residues 120 - 140 of human alpha-synuclein.
13. The method of claim 11 wherein the monoclonal antibody and second antibody are administered simultaneously.
14. The method of claim 11 wherein the monoclonal antibody and second antibody are administered the same day.
15. The method of claim 11 wherein the monoclonal antibody and second antibody are administered the same month.