Methods and compositions for treating or preventing pruritis

Abstract

The invention features therapeutic compositions comprising agents useful for the treatment or prevention of pruritis, and methods useful for identifying such agents.

1 - 3 . (canceled) 
     
     
         4 . A pharmaceutical composition labeled for the treatment or prevention of pruritis comprising an effective amount of an agent that inhibits the expression or biological activity of MrgX1. 
     
     
         5 - 6 . (canceled) 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the agent is an inhibitory nucleic acid molecule that hybridizes to at least a portion of an MrgX1 polynucleotide and is capable of reducing MrgX1 polypeptide or polynucleotide expression. 
     
     
         8 . The pharmaceutical composition of  claim 4 , wherein the inhibitory nucleic acid molecule is an siRNA, antisense oligonucleotide, or shRNA. 
     
     
         9 . An inhibitory nucleic acid molecule comprising a nucleic acid sequence that hybridizes to at least a portion of an MrgX1 or MrgA3 polynucleotide and is capable of inhibiting MrgX1 polypeptide or polynucleotide expression. 
     
     
         10 . The inhibitory polynucleotide of  claim 9 , wherein the inhibitory nucleic acid molecule is an siRNA, antisense oligonucleotide, or shRNA. 
     
     
         11 . A vector comprising the inhibitory nucleic acid molecule of  claim 9 . 
     
     
         12 . The vector of  claim 11 , wherein the inhibitory nucleic acid molecule is positioned for expression in a mammalian cell. 
     
     
         13 . A host cell comprising the vector of  claim 11 . 
     
     
         14 - 20 . (canceled) 
     
     
         21 . A method for identifying a candidate agent that reduces MrgA3 or MrgX1 expression, the method comprising:
 (a) contacting a cell expressing a MrgA3 or MrgX1 nucleic acid molecule with a candidate agent; and   (b) comparing MrgA3 or MrgX1 expression in he contacted cell with a reference level of expression, wherein a reduction in MrgA3 or MrgX1 expression identified the agent as reducing MrgA3 or MrgX1 expression.   
     
     
         22 . The method of  claim 21 , wherein the method identifies an agent that reduces MrgA3 or MrgX1 transcription or translation. 
     
     
         23 . A method for identifying a candidate agent that treats or prevents pruritis, the method comprising the steps of:
 (a) contacting a cell expressing a MrgA3 or MrgX1 polypeptide with a candidate agent; and   (b) detecting a reduction in MrgA3 or MrgX1 polypeptide level or biological activity in the cell contacted with the candidate agent relative to a reference level, wherein a reduction in MrgA3 or MrgX1 polypeptide level or biological activity identifies a candidate agent that treats or prevents pruritis.   
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 23 , wherein the agent is a MrgA3 or MrgX1 specific antibody, an aptamer, or a small compound. 
     
     
         26 - 44 . (canceled)