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 for prophylactic and therapeutic treatment of Parkinson's disease.

1 . A method of effecting prophylaxis 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 an antibody that specifically binds to an epitope within residues 110-130 of human alpha-synuclein, residues being numbered according to SEQ ID NO:1.  
     
     
         2 . The method of  claim 1  wherein the antibody binds to an epitope within residues 119-126 of human alpha-synuclein.  
     
     
         3 . The method of  claim 1 , wherein the disease is Parkinson's disease.  
     
     
         4 . The method of  claim 1 , wherein the antibody is a monoclonal antibody.  
     
     
         5 . The method of  claim 4 , wherein the antibody is a chimeric antibody, a human antibody, or a humanized antibody.  
     
     
         6 . 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.  
     
     
         7 . The method of  claim 5 , wherein the antibody is a humanized version of mouse monoclonal antibody 9E4 (ATCC accession number PTA-8221).  
     
     
         8 . The method of  claim 4 , wherein the antibody is an antibody of human IgG1 isotype.  
     
     
         9 . The method of  claim 2 , wherein the antibody is administered with a pharmaceutical carrier as a pharmaceutical composition.  
     
     
         10 . The method of  claim 9 , wherein the antibody is administered at a dosage of 0.0001 to 100 mg antibody/kg body weight.  
     
     
         11 . The method of  claim 9 , wherein the antibody is administered in multiple dosages over at least six months.  
     
     
         12 . The method of  claim 9 , wherein the antibody is administered intraperitoneally, orally, subcutaneously, intracranially, intramuscularly, topically, intranasally or intravenously.  
     
     
         15 . An anti-synuclein monoclonal antibody produced by hybridoma JH17.9E4.3.37.1.14.2 (ATCC accession number PTA-8221), hybridoma JH17.1H7.4.24.34 (ATCC accession number PTA-8220), or hybridoma JH22.11A5.6.29.70.54.16.14 (ATCC accession number PTA-8222).  
     
     
         16 . A cell of hybridoma JH17.9E4.3.37.1.14.2 (ATCC accession number PTA-8221), hybridoma JH17.1H7.4.24.34 (ATCC accession number PTA-8220), or hybridoma JH22.11A5.6.29.70.54.16.14 (ATCC accession number PTA-8222).