Therapeutic antibodies for treatment of neurodegeneration

Abstract

The invention provides therapeutic antibodies and methods for treatment of diseases associated with diseases associated with aggregation of α-synuclein, e.g., in the brain of a subject. Such methods provide administration of therapeutic antibodies to elicit a beneficial immunogenic response against aggregation of α-synuclein. The methods are particularly useful for prophylactic and therapeutic treatment of diseases associated with the formation of Lewy bodies, e.g., Parkinson's disease.

We claim: 
     
         1 . A method of treating a neurodegenerative disease comprising administering to a subject having or at risk of the disease a therapeutic antibody comprising the VL CDRs of SEQ ID NO:1, SEQ NO:2 and SEQ NO: 3 and comprising the VH CDRs of SEQ ID NO:4, SEQ NO:5 and SEQ NO: 6. 
     
     
         2 . The method of  claim 1 , wherein the therapeutic antibody is a monoclonal antibody. 
     
     
         3 . The method of  claim 2 , wherein the therapeutic antibody is a humanized monoclonal antibody. 
     
     
         4 . The method of  claim 1 , wherein the therapeutic antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic antibody is an Fv, scFv, Fab, F(ab′)2, or Fab′. 
     
     
         6 . The method of  claim 1 , wherein the therapeutic antibody comprises a VH region having substantial identity to SEQ NO:8. 
     
     
         7 . The method of  claim 1 , wherein the antibody is administered at a dosage of 0.0001 to 100 mg antibody/kg body weight. 
     
     
         8 . The method of  claim 1 , wherein the therapeutic antibody is administered with a pharmaceutical carrier. 
     
     
         9 . The method of  claim 1 , wherein the therapeutic antibody is administered in multiple dosages over at least six months. 
     
     
         10 . The method of  claim 1 , wherein the antibody is administered at a dosage of 0.0001 to 100 mg antibody/kg body weight. 
     
     
         11 . The method of  claim 1 , wherein the therapeutic antibody is administered with a pharmaceutical carrier. 
     
     
         12 . The method of  claim 1 , wherein the therapeutic antibody is administered in multiple dosages over at least six months. 
     
     
         13 . The method of  claim 1 , wherein the neurodegenerative disease is Parkinson's disease. 
     
     
         14 . The method of  claim 1 , wherein the therapeutic antibody is administered to an individual with a known genetic risk of α-synuclein aggregation. 
     
     
         15 . The method of  claim 14 , wherein the individual has a mutation in a gene selected from Synuclein, Parkin, UCHLI, and CYP2D6. 
     
     
         16 . The method of  claim 14 , wherein the therapeutic antibody is administered prophylactically.