Modulators Of NOD2 Signalling

Abstract

The present invention relates to intracellular signaling molecules, in particular the Nod2 protein and nucleic acids encoding the Nod2 protein. The present invention provides methods of identifying modulators of Nod2 signaling. In particular, the present invention additionally provides methods of screening immune modulators such as adjuvants using Nod2. The present invention further provides methods of altering Nod2 signaling.

1 - 29 . (canceled) 
     
     
         30 . An assay method for determining a treatment therapeutic level in a subject, said assay method comprising:
 determining said subject's Nod2 status by determine the presence or absence of one or more Nod2 variants selected from the group consisting of SEQ ID NOs: 54, 56, 58, and 60; and   recommending a treatment based on said subject's Nod2 status.   
     
     
         31 . The assay method of  claim 30 , wherein said subject has Crohn's disease. 
     
     
         32 . The assay method of  claim 30 , wherein said therapeutic is delivered to the gut. 
     
     
         33 . The assay method of  claim 30 , wherein said therapeutic is delivered to the blood. 
     
     
         34 . The assay method of  claim 30 , wherein said therapeutic provides increased Nod2 signaling. 
     
     
         35 . The assay method of  claim 30 , wherein said therapeutic increases Nod2 activity in said subject that lacks a response or has a diminished response to bacterial muropeptides. 
     
     
         36 . The assay method of  claim 30 , wherein said treatment is a pharmaceutical composition. 
     
     
         37 . The assay method of  claim 30 , wherein said pharmaceutical composition is formulated in a member selected from the group consisting of a tablet, a pill, a capsule, a liquid, a gel, a syrup, a slurry, and a suspension. 
     
     
         38 . The assay method of  claim 30 , wherein said treatment comprises a colonic drug delivery system. 
     
     
         39 . The assay method of  claim 38 , wherein said colonic drug delivery system is a member selected from the group consisting of an enema, a rectal foam, a delayed release oral formulation, and an enteric coating. 
     
     
         40 . The assay method of  claim 30 , wherein said treatment comprises administration of MDP or an analog thereof. 
     
     
         41 . The assay method of  claim 30 , wherein said treatment comprises administration of an inhibitors or antagonist of Nod2 activity. 
     
     
         42 . The assay method of  claim 30 , wherein said treatment administration is a member selected form the group consisting of oral, transmucosal, parenteral and intranasal. 
     
     
         43 . The assay method of  claim 30 , wherein said method further comprises a prognosis of Crohn's disease in said subject based on the presence or absence a response to a bacterial muropeptide. 
     
     
         44 . An assay method for the prognosis of Crohn's disease in a subject, said method comprising:
 determining said subject's Nod2 status by determine the presence or absence of one or more Nod2 variants selected from the group consisting of SEQ ID NOs: 54, 56, 58, and 60, wherein said Nod2 variant is defective in responding to bacterial muropeptide;   recommending a treatment based on said subject's Nod2 status; and   determining the presence or absence of a response to a bacterial muropeptide after said treatment.   
     
     
         45 . The assay method of  claim 45 , wherein said treatment is delivered to the gut. 
     
     
         46 . The assay method of  claim 45 , wherein said treatment is delivered to the blood. 
     
     
         47 . The assay method of  claim 45 , wherein said treatment provides increased Nod2 signaling. 
     
     
         48 . The assay method of  claim 45 , wherein said treatment comprises administration of MDP or an analog thereof. 
     
     
         49 . The assay method of  claim 45 , wherein said treatment comprises a colonic drug delivery system.