Antibodies to Alpha Synuclein

Abstract

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

1 . A method of screening for an agent having a pharmacological activity useful for treating a Lewy Body Disease (LBD) comprising:
 contacting the agent with phosphorylated alpha-synuclein or a phosphorylated fragment thereof, wherein the fragment is characterized by presence of at least 100 contiguous amino acids of intact alpha-synuclein and a deletion of 1-11 contiguous amino acids from the C-terminus of intact alpha-synuclein;   determining the rate or extent of aggregation of the alpha synuclein or fragment of alpha-synuclein, wherein a reduction in the rate or extent of aggregation relative to a control lacking the agent indicates the agent has the pharmacological activity.   
     
     
         2 - 34 . (canceled) 
     
     
         35 . A method of detecting presence or susceptibility to an LBD in a patient, comprising
 detecting a level of a fragment of alpha-synuclein in body fluid, wherein the fragment is SN1-115, SN1-133 or SN1-135 numbered according to SEQ ID NO:1;   a level greater than a baseline level in undiseased individuals indicating presence or susceptibility to LBD.   
     
     
         36 . An antibody that specifically binds to a fragment of alpha-synuclein, wherein the fragment is SN1-115, SN116-140, SN1-133, SN1-135, SN134-140 or SN136-140 numbered according to SEQ ID NO:1; without specifically binding to full-length alpha synuclein. 
     
     
         37 . The antibody of  claim 36  that is a human antibody. 
     
     
         38 . The antibody of  claim 36  that is a humanized antibody. 
     
     
         39 . The antibody of  claim 36  that is a monoclonal antibody. 
     
     
         40 . The antibody of  claim 36  having human isotype IgG1. 
     
     
         41 . The antibody of  claim 36  designated 12C6 or 7G8. 
     
     
         42 - 52 . (canceled)