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 treating, reducing the risk of, lessening the severity of, or delaying the outset of 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 an antibody that specifically binds to an epitope within residues 118-126 of intact human alpha-synuclein, residues being numbered according to SEQ ID NO: 1.
2. The method of claim 1 , wherein the disease is Parkinson's disease.
3. The method of claim 1 , wherein the antibody is a monoclonal antibody.
4. The method of claim 3 , wherein the antibody is a chimeric antibody, a human antibody, or a humanized antibody.
5. The method of claim 4 , wherein the antibody is monoclonal antibody 9E4 (ATCC accession number PTA-8221) or humanized or chimeric 9E4.
6. The method of claim 3 , wherein the antibody is an antibody of human IgG1 isotype.
7. The method of claim 1 wherein the antibody competes with mouse monoclonal antibody 9E4 (ATCC accession number PTA-8221) for binding to human alpha-synuclein.
8. The method of claim 1 , wherein the antibody is administered with a pharmaceutical carrier as a pharmaceutical composition.
9. The method of claim 8 , wherein the antibody is administered at a dosage of 0.0001 to 100 mg antibody/kg body weight.
10. The method of claim 8 , wherein the antibody is administered in multiple dosages over at least six months.
11. The method of claim 8 , wherein the antibody is administered intraperitoneally, orally, subcutaneously, intracranially, intramuscularly, topically, intranasally or intravenously.
12. The method of claim 1 , wherein the antibody is administered by a peripheral route.
13. The method of claim 1 , wherein the antibody is administered at a dose of 1-10 mg/kg.
14. The method of claim 1 , wherein the antibody is humanized 9E4 and comprises the CDRs of mouse monoclonal 9E4 (ATCC accession number PTA-8221) as defined by Kabat.
15. The method of claim 1 , wherein the antibody is humanized 9E4 and comprises the CDRs of mouse 9E4 (ATCC accession number PTA-8221) as defined by Chothia.