Compositions and Methods for Identifying and Treating Dystonia Disorders

Abstract

The present disclosure provides methods and compositions for the treatment, identification, diagnosis, and prognosis of dystonia, or dystonia related disorders.

1 .- 27 . (canceled) 
     
     
         28 . A method of monitoring disease progression, the method comprising:
 obtaining a first biological sample from a subject having dystonia;   determining the expression level of one or more biomarkers in the first biological sample, wherein the one or more biomarkers comprise CreP, RAP1A, MAP2K5, or any combination thereof;   treating the subject by administering an agent;   obtaining a second biological sample from the subject;   determining the expression level of the same one or more biomarkers in the second biological sample;   comparing the expression level of the one or more biomarkers in the first and second biological samples;   determining that the subject has improved dystonia when the level of the one or more biomarkers in the second sample is decreased relative to the level of the same one or more biomarkers in the first sample; and   continuing treating dystonia by administering the agent.   
     
     
         29 . The method of  claim 28 , wherein the one or more biomarkers comprises CreP 
     
     
         30 . The method of  claim 28 , wherein the one or more biomarkers comprises RAP1A. 
     
     
         31 . The method of  claim 28 , wherein the one or more biomarkers comprises MAP2K5. 
     
     
         32 . The method of  claim 28 , further comprising determining the level of delta-E Torsin1a mislocalization in the first biosample and the second biosample, and comparing the levels delta-E Torsin1a mislocalization in the first and second biological samples. 
     
     
         33 . The method of  claim 28 , wherein the subject is a human. 
     
     
         34 . The method of  claim 28 , wherein the biological sample comprise tissues, cells, biopsies, blood, cerebrospinal fluid, lymph, serum, plasma, urine, saliva, mucus, tears, or any combination thereof. 
     
     
         35 . The method of  claim 28 , wherein the dystonia is inherited, familial, or sporadic. 
     
     
         36 . The method of  claim 28 , wherein the agent is salubrinal or Sal-003. 
     
     
         37 . The method of  claim 28 , wherein the agent is one or more HIV protease inhibitors. 
     
     
         38 . The method of  claim 37 , wherein the one or more HIV protease inhibitors comprise ritonavir, lopinavir, saquinavir, nelfinavir, or indinavir. 
     
     
         39 . A method of monitoring disease progression, the method comprising:
 obtaining a first biological sample from a subject having dystonia;   determining the level of delta-E Torsin1a mislocalization in the first biosample;   treating the subject by administering an agent;   obtaining a second biological sample from the subject;   determining the level of delta-E Torsin1a mislocalization in the second biological sample;   comparing the level of delta-E Torsin1a mislocalization in the first and second biological samples;   determining that the subject has improved dystonia when the delta-E Torsin1a mislocalization in the second biological sample is decreased relative to the level of delta-E Torsin1a mislocalization in the first biological sample; and   continuing treating dystonia by administering the agent.   
     
     
         40 . The method of  claim 39 , further comprising determining the expression level of one or more biomarkers in the first and second biological samples, wherein the one or more biomarkers comprises CreP, RAP1A, MAP2K5, or any combination thereof. 
     
     
         41 . The method of  claim 40 , further comprising comparing the level of the one or more biomarkers in the first and second biological samples. 
     
     
         42 . The method of  claim 39 , wherein the subject is a human. 
     
     
         43 . The method of  claim 39 , wherein the biological samples comprise tissues, cells, biopsies, blood, cerebrospinal fluid, lymph, serum, plasma, urine, saliva, mucus, tears, or any combination thereof. 
     
     
         44 . The method of  claim 39 , wherein the dystonia is inherited, familial, or sporadic. 
     
     
         45 . The method of  claim 39 , wherein the agent is salubrinal or Sal-003. 
     
     
         46 . The method of  claim 39 , wherein the agent is one or more HIV protease inhibitors. 
     
     
         47 . The method of  claim 46 , wherein the one or more HIV protease inhibitors comprise ritonavir, lopinavir, saquinavir, nelfinavir, or indinavir.