Novel Target for Regulating Multiple Sclerosis

Abstract

Methods are provided for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1 (CMKLR1). Methods are also provided for screening for agents that find use in treating demyelinating inflammatory disease in a subject.

What is claimed is: 
     
         1 . A method of decreasing demyelinating inflammatory disease in a subject, the method comprising:
 administering to said subject an effective amount of a chemokine-like receptor 1 (CMKLR1) antagonist.   
     
     
         2 . The method of  claim 1 , wherein said CMKLR1 antagonist binds to CMKLR1. 
     
     
         3 . The method of  claim 2 , wherein said CMKLR1 antagonist comprises a natural or altered domain derived from a natural ligand of CMKLR1. 
     
     
         4 . The method of  claim 1 , wherein said CMKLR1 antagonist is a polypeptide. 
     
     
         5 . The method of  claim 4 , wherein said polypeptide is an antibody or antigen binding fragment thereof. 
     
     
         6 . The method of  claim 1 , wherein said CMKLR1 modulatory agent is an siRNA. 
     
     
         7 . The method of  claim 1 , wherein said antagonizing agent inhibits ligand-induced signaling from CMKLR1 in a cell. 
     
     
         8 . The method of  claim 1 , wherein said antagonizing agent reduces the expression of CMKLR1 in a cell. 
     
     
         9 . The method of  claim 1 , wherein said antagonizing agent inhibits transcription of CMKLR1. 
     
     
         10 . A method of screening for an agent that decreases demyelinating inflammatory disease in a subject, said method comprising:
 contacting said agent to a cell expressing CMKLR1; and   evaluating whether said agent antagonizes CMKLR1 activity.   
     
     
         11 . The method of  claim 10 , wherein said CMKLR1 activity is selected from the group consisting of: chemotaxis, activation of a signaling pathway component, activation of gene or reporter gene expression, and expression of CMKLR1. 
     
     
         12 . The method of  claim 10 , wherein said method is a high throughput screening method. 
     
     
         13 . The method of  claim 10 , wherein said cell naturally expresses CMKLR1 or is genetically engineered to express CMKLR1. 
     
     
         14 . The method of  claim 10 , further comprising validating said agent as a demyelinating inflammatory disease regulator in an animal model.