Ice-cleaved alpha-synuclein as a biomarker

Abstract

The present disclosure provides ICE-cleaved alpha-synuclein fragments as biomarkers for alpha-synuclein-associated disease or disorder and/or for ICE-regulator therapy.

What is claimed: 
     
         1 - 16 . (canceled) 
     
     
         17 . A method of treating a patient suffering from or susceptible to a synucleinopathy disease, disorder, or condition, comprising:
 administering to the patient a composition comprising an amount of an ICE inhibitor sufficient to inhibit cleavage of α-synuclein by ICE.   
     
     
         18 . The method of  claim 17 , wherein the patient has been determined to display a, within a sample from the patient, a ratio of a fragment to full length α-synuclein that is elevated as compared to a reference ratio. 
     
     
         19 . The method of  claim 18 , wherein the fragment is about 120 amino acids in length. 
     
     
         20 . The method of  claim 18 , wherein the fragment is 115 amino acids in length. 
     
     
         21 . The method of  claim 18 , wherein the fragment is 119 amino acids in length. 
     
     
         22 . The method of  claim 18 , wherein the fragment is 121 amino acids in length. 
     
     
         23 . The method of  claim 18 , wherein the fragment is about 20 amino acids in length. 
     
     
         24 . The method of  claim 17 , wherein the synucleinopathy disease, disorder or condition is Parkinson's disease, dementia, or multiple system atrophy. 
     
     
         25 . The method of  claim 24 , wherein the Parkinson's disease is an autosomal-dominant Parkinson's disease. 
     
     
         26 . The method of  claim 24 , wherein the synucleinopathy disease, disorder or condition is characterized by the presence of Lewy bodies. 
     
     
         27 . The method of claim of  18 , wherein the fragment of alpha synuclein is undetectable in the reference standard. 
     
     
         28 . The method of  claim 17 , wherein the ICE inhibitor is a small molecule, peptide, or nucleic acid. 
     
     
         29 . The method of  claim 28 , wherein the ICE inhibitor is of one of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         30 . The method of  claim 17 , wherein the administered composition inhibits cleavage of a full length α-synuclein polypeptide into at least two fragments having lengths of about 120 amino acids and about 20 amino acids. 
     
     
         31 . The method of  claim 17 , wherein the administered composition inhibits proteolytic cleavage at or around a site corresponding to residue 120 in full length α-synuclein. 
     
     
         32 . The method of  claim 17 , wherein the administered composition causes a higher ratio of full-length to cleaved fragments of α-synuclein as compared to a control. 
     
     
         33 . The method of  claim 32 , wherein the displayed ratio is one, two, three, four, five, six, seven, eight, nine, or ten times higher than the reference ratio. 
     
     
         34 . The method of  claim 32 , wherein the displayed ratio is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% higher than the reference ratio.