Alpha B-Crystallin as a Therapy for Ischemia or Inflammation

Abstract

The invention provides methods for treating inflammatory diseases by administering to the subject an effective amount of an agent that provides alpha B-crystallin activity, where the dose is effective to suppress or prevent initiation, progression, or relapses of disease, including the progression of established disease. In some embodiments, the methods of the invention comprise administering to a subject having a pre-existing inflammatory disease condition, an effective amount of alpha B-crystallin protein, to suppress or prevent relapses of the disease.

What is claimed is: 
     
         1 . A method for inhibiting an ischemic disease in a patient, the method comprising:
 administering to said patient a therapeutically effective dose of an agent that increases alpha B-crystallin activity.   
     
     
         2 . The method of  claim 1 , wherein the agent is an alpha B-crystallin protein or an active fragment thereof. 
     
     
         3 . The method of  claim 2 , wherein the agent is administered systemically. 
     
     
         4 . The method of  claim 3 , wherein a route of systemic administration is selected from the group consisting of intraperitoneal, intravenous, intramuscular and subcutaneous administration. 
     
     
         5 . The method of  claim 4 , wherein administration is intravenous. 
     
     
         6 . The method of  claim 1 , wherein the inflammatory disease is an inflammatory neurological disease. 
     
     
         7 . The method of  claim 6 , wherein the inflammatory neurological disease is a demyelinating disease. 
     
     
         8 . The method according to  claim 7 , wherein said disease is multiple sclerosis or neuromyelitis optica. 
     
     
         9 . The method of  claim 6 , wherein the inflammatory neurological disease is Parkinson's disease. 
     
     
         10 . The method of  claim 6 , wherein the inflammatory neurological disease is Alzheimer's disease. 
     
     
         11 . The method of  claim 6 , wherein the inflammatory neurological disease is amyotrophic lateral sclerosis. 
     
     
         12 . The method of  claim 1 , wherein the inflammatory disease is atherosclerosis, myocardial infarction, stroke, or peripheral occlusive arterial disease. 
     
     
         13 . The method of  claim 1 , wherein the inflammatory disease is rheumatoid arthritis. 
     
     
         14 . The method of  claim 1 , wherein the mammal is diagnosed as having the autoimmune disease prior to the administering step. 
     
     
         15 . The method of  claim 1 , further comprising:
 monitoring the activation of T cells in tissues affected by the autoimmune disease.   
     
     
         16 . The method of  claim 11 , further comprising:
 monitoring the secretion of pro-inflammatory cytokines in activated T cells in tissues affected by the autoimmune disease, wherein a decrease in secretion is indicative that a therapeutically effective dose of alpha B-crystallin has been administered.   
     
     
         17 . The method of  claim 16 , further comprising monitoring the expression and/or phosphorylation of p38MAPK or ERK, wherein a decrease in expression or phosphorylation is indicative that a therapeutically effective dose of alpha B-crystallin has been administered. 
     
     
         18 . The method according to  claim 2 , wherein said agent is a fusion polypeptide of αBC and an immunoglobulin Fc polypeptide. 
     
     
         19 . The method according to  claim 1 , wherein said agent is a nucleic acid that encodes alpha B-crystallin. 
     
     
         20 . The method of  claim 1 , wherein the agent is administered in a combination therapy with a second antigen-specific or non-antigen specific agent. 
     
     
         21 . The method of  claim 1 , wherein the agent is administered within 12 hours of onset of a stroke or within 12 hours of onset of optic nerve ischemia.