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 - 52 . (canceled) 
     
     
         53 . An antibody that specifically binds to a fragment of alpha-synuclein without specifically binding to full-length alpha synuclein as defined in SEQ ID NO.1, wherein said fragment is present in patients with Lewy Body Disease and is characterized by presence of at least 100 contiguous amino acids of intact alpha-synuclein and a deletion of 1-25 contiguous amino acids from the C-terminus of intact alpha-synuclein, wherein the antibody is preferably a human or humanized antibody, more preferably of human isotype IgG1, or a fragment of less than 20 amino acids of alpha synuclein that induces such an antibody, wherein the fragment that induces the antibody includes the C-terminus of the truncated fragment present in patients with Lewy Body Disease. 
     
     
         54 . The antibody of  claim 53  for use in diagnosing the presence or susceptibility to a LBD wherein the antibody is to be administered to a patient and the level of binding of the antibody in the patient is to be determined, wherein a higher level of binding relative to a base line level in undiseased individuals indicates presence or susceptibility to the LBD. 
     
     
         55 . The antibody of  claim 53 , or the fragment of less than 20 amino acids of alpha synuclein that induces the antibody of  claim 53 , for use in the treatment or prophylaxis of Lewy body disease. 
     
     
         56 . An antibody that specifically binds to a 1-122 or 1-119 fragment of alpha-synuclein, without specifically binding to full-length alpha-synuclein as defined in SEQ ID No.1, or a fragment that induces this antibody wherein the fragment that induces the antibody has less than 20 amino acids of alpha-synuclein and includes the C-terminus of the 1-122 or 1-119 fragment of alpha-synuclein. 
     
     
         57 . The antibody of  claim 56  that is a human or humanized antibody, preferably of human isotype IgG1. 
     
     
         58 . The antibody of  claim 56  or the fragment that induces the antibody of  claim 56 , for use in the treatment or prophylaxis of Lewy body disease. 
     
     
         59 . The antibody of  claim 57  or the fragment that induces the antibody of  claim 56 , for use in the treatment or prophylaxis of Lewy body disease. 
     
     
         60 . A method of diagnosing the presence or susceptibility to a LBD wherein the antibody of  claim 56  is to be administered to a patient and the level of binding of the antibody in the patient is to be determined, wherein a higher level of binding relative to a base line level in undiseased individuals indicates presence or susceptibility to the LBD. 
     
     
         61 . A method of diagnosing the presence or susceptibility to a LBD wherein the antibody of  claim 57  is to be administered to a patient and the level of binding of the antibody in the patient is to be determined, wherein a higher level of binding relative to a base line level in undiseased individuals indicates presence or susceptibility to the LBD.