Treatment and delay of outset 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 immunogenic fragment of alpha-synuclein consisting of 5-9 contiguous residues from between residues 118-126 of human alpha synuclein (SEQ ID NO:1) effective to induce an immunogenic response comprising antibodies that specifically bind to an epitope within residues 118-126 of SEQ ID NO: 1, thereby reducing the risk of, lessening the severity of, delaying the outset of or treating the disease.
2. The method of claim 1 , wherein the immunogenic fragment is SN118-126.
3. The method of claim 1 , wherein the immunogenic fragment is linked to a carrier to form a conjugate.
4. The method of claim 3 , wherein the carrier is a heterologous polypeptide.
5. The method of claim 3 , wherein the carrier is a tetanus toxoid.
6. The method of claim 3 , wherein the carrier is a diphtheria toxoid.
7. The method of claim 4 , wherein the heterologous polypeptide comprises the amino acid sequence AKXVAAWTLKAAA (SEQ ID NO:12).
8. The method of claim 1 , wherein the disease is Parkinson's disease.
9. The method of claim 1 , wherein the immunogenic fragment is administered with a pharmaceutical carrier as a pharmaceutical composition.
10. The method of claim 1 , wherein the immunogenic fragment is administered in combination with an adjuvant.
11. The method of claim 10 , wherein the adjuvant is pharmaceutically acceptable for human administration.
12. The method of claim 10 , wherein the adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, alum, CpG, GM-CSF and M-CSF.
13. The method of claim 1 , wherein the immunogenic fragment is administered at a dosage of 1-500 μg per injection.
14. The method of claim 1 , wherein the immunogenic fragment is administered in multiple dosages over at least six months.
15. The method of claim 1 , wherein the immunogenic fragment is administered intraperitoneally, subcutaneously, intramuscularly, intranasally or intravenously.