Methods for diagnosing huntington's disease

Abstract

The disclosure provides methods for the diagnosis of Huntington's disease. In some embodiments, the method comprises detecting one or more repeat associated non-ATG (RAN) proteins in a biological sample.

1 - 28 . (canceled) 
     
     
         29 . An in vitro method of detecting one or more RAN proteins, the method comprising:
 (a) contacting a biological sample obtained from a subject with one or more anti-repeat-associated non-ATG (anti-RAN) protein antibodies that target a RAN protein selected from poly-Alanine, poly-Leucine, poly-Serine, and poly-Cysteine; and   (b) detecting binding of the one or more anti-RAN protein antibodies to one or more RAN proteins in the sample.   
     
     
         30 . The method of  claim 29 , wherein the biological sample comprises blood, serum, brain tissue, spinal tissue, or cerebrospinal fluid (CSF). 
     
     
         31 . The method of  claim 30 , wherein the biological sample comprises blood or CSF. 
     
     
         32 . The method of  claim 29 , wherein the subject is a human. 
     
     
         33 . The method of  claim 29 , wherein the subject has or is suspected of having Huntington's disease. 
     
     
         34 . The method of  claim 33 , wherein the subject comprises a HTT gene having at least 35 CAG repeats. 
     
     
         35 . The method of  claim 34 , wherein one or more RAN proteins are translated from the HTT gene. 
     
     
         36 . The method of  claim 29 , wherein the sample has been treated by one or more antigen retrieval techniques prior to the step of contacting. 
     
     
         37 . The method of  claim 36 , wherein the antigen retrieval technique comprises heat-induced epitope retrieval (HIER) or protease-induced epitope retrieval (PIER). 
     
     
         38 . The method of  claim 37 , wherein the antigen retrieval technique comprises heat-induced epitope retrieval (HIER) and protease-induced epitope retrieval (PIER). 
     
     
         39 . The method of  claim 29 , wherein one or more of the anti-RAN protein antibodies binds to a C-terminal region of the RAN protein. 
     
     
         40 . The method of  claim 39 , wherein the C-terminal region of the RAN protein bound by the anti-RAN antibody comprises the sequence set forth in SEQ ID NO: 19, 20, 21, or 22. 
     
     
         41 . The method of  claim 29 , wherein the one or more anti-RAN protein antibodies are polyclonal antibodies. 
     
     
         42 . The method of  claim 41 , wherein the one or more anti-RAN protein antibodies are mouse antibodies. 
     
     
         43 . The method of  claim 29 , wherein the detecting comprises immunoblot analysis, Western blot analysis, immunohistochemistry, or ELISA.