Methods of treatment of hla-b27 related inflammatory diseases and compositions related to same

Abstract

The present disclosure provides methods and compositions for treatment of an HLA-B27-associated autoimmune inflammatory disorder by administration of nucleic acid encoding HSP90 or an active fragment thereof.

What is claimed is: 
     
         1 . A method of treating or preventing an autoimmune inflammatory disease in an HLA-B27 positive subject, the method comprising:
 administering to a subject having or at risk of an autoimmune inflammatory disease and who is positive for HLA-B27 a composition comprising a nucleic acid molecule encoding a mammalian heat shock protein 90 (HSP90), or an active fragment thereof, wherein the nucleic acid molecule is operatively linked to one or more transcription control sequences,   wherein the administering treats the inflammatory disease in the subject.   
     
     
         2 . The method of  claim 1 , wherein the autoimmune inflammatory disease is an inflammatory joint disease. 
     
     
         3 . The method of  claim 2 , wherein the inflammatory joint disease is a spondyloarthropathy. 
     
     
         4 . The method of  claim 3 , wherein the spondyloarthropathy is anklyosing spondylitis, reactive arthritis, psoriatic arthritis or enteropathic arthritis. 
     
     
         5 . The method of  claim 2 , wherein the inflammatory joint disease is juvenile spondarthritis, undifferentiated spondarthritis or isolated peripheral enthesitis. 
     
     
         6 . The method of  claim 1 , wherein the autoimmune inflammatory disease is an ocular disorder. 
     
     
         7 . The method of  claim 6 , wherein the ocular disorder is uveitis or age-related macular degeneration. 
     
     
         8 . The method of  claim 7 , wherein the uveitis is acute anterior uveitis or posterior uveitis. 
     
     
         9 . The method of  claim 1 , wherein the autoimmune inflammatory disease is an inflammatory disease of the gastrointestinal tract. 
     
     
         10 . The method of  claim 9 , wherein the autoimmune inflammatory disease is inflammatory bowel disease, ulcerative colitis, or Crohn's disease. 
     
     
         11 . The method of  claim 1 , wherein the autoimmune inflammatory disease is Behcet disease. 
     
     
         12 . The method of  claim 1 , wherein the autoimmune inflammatory disease is a cardiovascular disease. 
     
     
         13 . The method of any one of  claims 1 - 12 , wherein the subject is at risk of the autoimmune inflammatory disorder. 
     
     
         14 . The method of any one of  claims 1 - 12 , wherein the subject has the autoimmune inflammatory disorder. 
     
     
         15 . The method of any one of  claims 1 - 14 , wherein the mammalian HSP90 is human HSP90. 
     
     
         16 . The method of  claim 15 , wherein the subject is a human. 
     
     
         17 . The method of any one of  claims 1 - 16 , wherein said administering is by injection. 
     
     
         18 . The method of  claim 17 , wherein administering is by intramuscular injection. 
     
     
         19 . The method of any one of  claims 1 - 18 , wherein the composition is administered in an amount of from about 0.005 mg/kg to about 1 mg/kg of the nucleic acid molecule encoding the mammalian HSP90, or an active fragment thereof, to the body weight of the subject. 
     
     
         20 . The method of  claim 19 , wherein the composition is administered in an amount of from about 0.01 mg/kg to about 0.5 mg/kg of the nucleic acid molecule encoding the mammalian HSP90, or an active fragment thereof, to the body weight of the subject. 
     
     
         21 . The method of  claim 19 , wherein the composition is administered in an amount of from about 0.10 mg/kg to about 0.30 mg/kg of the nucleic acid molecule encoding the mammalian HSP90, or an active fragment thereof, to the body weight of the subject. 
     
     
         22 . The method of any one of  claims 1 - 21 , wherein the composition is administered weekly. 
     
     
         23 . The method of any one of  claims 1 - 22 , wherein the composition is administered for a period of at least 4 weeks. 
     
     
         24 . The method of any one of  claims 1 - 23 , wherein the nucleic acid molecule is not encapsulated. 
     
     
         25 . The method of any one of  claims 1 - 24 , wherein the nucleic acid molecule is not contained in a virus. 
     
     
         26 . The method of any one of  claims 1 - 25 , wherein the composition comprises a pharmaceutically acceptable alkali metal salt. 
     
     
         27 . The method of  claim 26 , wherein the pharmaceutically acceptable alkali metal salt is sodium chloride. 
     
     
         28 . The method of any one of  claims 1 - 27 , wherein the composition comprises a delivery vehicle selected from the group consisting of a liposome, a micelle, and an emulsion. 
     
     
         29 . The method of any one of  claims 1 - 27 , wherein the composition comprises a lipid particle. 
     
     
         30 . The method of any one of  claims 1 - 27 , wherein the composition comprises a catioinic lipid, polyethylene glycol, polylysine, poloxamer, chitosan, polyL glutamate, or poly(lactide-co-glycolide) (PLG). 
     
     
         31 . A composition comprising an HSP90-encoding nucleic acid for use in treatment of an autoimmune inflammatory disorder in an HLA-B27 positive subject. 
     
     
         32 . Use of an HSP90-encoding nucleic acid in the manufacture of a medicament for in treatment of an autoimmune inflammatory disorder in an HLA-B27 positive subject.