Prevention and treatment of synucleinopathic and amyloidogenic disease

Abstract

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 prophylactic and therapeutic treatment of Parkinson's disease.

1 - 32 . (canceled) 
     
     
         33 . 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 5-10 contiguous residues of alpha synuclein effective to induce an immunogenic response comprising antibodies that specifically bind to an epitope within residues 91-99 of human alpha-synuclein, residues being numbered according to SEQ ID NO: 1, thereby reducing the risk of, lessening the severity of, delaying the outset of or treating the disease. 
     
     
         34 . The method of  claim 33 , wherein the immunogenic fragment is SN91-99. 
     
     
         35 . The method of  claim 33 , wherein the immunogenic fragment is linked to a carrier to form a conjugate. 
     
     
         36 . The method of  claim 35 , wherein the carrier is a heterologous polypeptide. 
     
     
         37 . The method of  claim 35 , wherein the carrier is a tetanus toxoid. 
     
     
         38 . The method of  claim 35 , wherein the carrier is a diphtheria toxoid. 
     
     
         39 . The method of  claim 36 , wherein the heterologous polypeptide comprises the amino acid sequence AKXVAAWTLKAAA (SEQ ID NO:12). 
     
     
         40 . The method of  claim 33 , wherein the disease is Parkinson's disease. 
     
     
         41 . The method of  claim 33 , wherein the immunogenic fragment is administered with a pharmaceutical carrier as a pharmaceutical composition. 
     
     
         42 . The method of  claim 33 , wherein the immunogenic fragment is administered in combination with an adjuvant. 
     
     
         43 . The method of  claim 42 , wherein the adjuvant is pharmaceutically acceptable for human administration. 
     
     
         44 . The method of  claim 42 , wherein the adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, alum, CpG, GM-CSF and M-CSF. 
     
     
         45 . The method of  claim 33 , wherein the immunogenic fragment is administered at a dosage of 1-500 μg per injection. 
     
     
         46 . The method of  claim 33 , wherein the immunogenic fragment is administered in multiple dosages over at least six months. 
     
     
         47 . The method of  claim 33 , wherein the immunogenic fragment is administered intraperitoneally, subcutaneously, intramuscularly, intranasally or intravenously. 
     
     
         48 . 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 a polypeptide comprising an immunogenic fragment of alpha-synuclein effective to induce an immunogenic response comprising antibodies that specifically bind to an epitope within residues 1-40 of human alpha-synuclein, residues being numbered according to SEQ ID NO: 1, thereby effecting prophylaxis or treatment of the disease. 
     
     
         49 . The method of  claim 48 , wherein the immunogenic fragment comprises SN1-5 and contains no more than 40 contiguous residues in total of alpha synuclein, residues being numbered according to SEQ ID NO: 1. 
     
     
         50 . The method of  claim 48 , wherein the immunogenic fragment is selected from the group consisting of consisting of SN1-5, SN1-6, SN1-7, SN1-8, SN1-9, SN1-10, SN1-11, SN1-12, SN1-13, and SN1-14 SN1-15, SN1-16, SN1-17, SN1-18, SN1-19, and SN1-20. 
     
     
         51 . The method of  claim 48  comprising:
 administering to a patient having or at risk of the disease a polypeptide comprising an immunogenic fragment of alpha-synuclein effective to induce an immunogenic response comprising antibodies that specifically bind to an epitope within residues 1-20 of human alpha-synuclein, residues being numbered according to SEQ ID NO:1, 
 wherein the immunogenic fragment of alpha-synuclein is free of at least residues 25-69, residues 70-140, residues 41-140, or residues 25-140 of alpha synuclein, 
 thereby effecting prophylaxis or treatment of the disease. 
 
     
     
         52 . The method of  claim 51 , wherein the immunogenic fragment is linked to a carrier to form a conjugate. 
     
     
         53 . A pharmaceutical composition comprising a first immunogenic fragment of alpha-synuclein, said first fragment effective to induce an immunogenic response comprising antibodies that specifically bind to an epitope within residues 1-20 of human alpha-synuclein, and a pharmaceutical carrier.