Method of selecting agents for the treatment of pain using neuronal differentiation

Abstract

The present invention is based on the seminal concept of treating pain by promoting neuronal differentiation. The invention provides a screening method for the selection of agents for the purpose of treating pain, utilizing neuronal differentiation as selection criteria. Methods and libraries available for screening for the selection of candidate agents are provided.

1 . A screening method for the identification, optimization, development and selection of agents having the ability to treat pain in an individual, comprising of assays that analyze and optimize the ability of these agents to induce or promote neuronal differentiation. 
     
     
         2 . The method of  claim 1 , wherein the ability of an agent to treat pain is measured in a human or in a mammal by administering that agent, alone or in combination with other agents, in an amount sufficient to cause a detectable decrease in pain, as determined by a pain or nociception measurement method. 
     
     
         3 . The method of  claim 1 , wherein neuronal differentiation is measured as a change in cellular properties selected from the group consisting of anatomical, electrophysiological, gene expression, RNA expression, protein expression, chemical, biochemical, immunofluorescence, immunochemical, immunological, physiological, spectroscopic, caloric, optic, metabolic, and secretory properties of a cell, measured in cell culture or in a mammal. 
     
     
         4 . The method of  claim 1 , wherein the agent is an agonist, antagonist, partial agonist or inverse agonist of a receptor selected from the group consisting of TrkA, TrkB, TrkC, p75trk, a CNTF receptor, an EGF receptor, a FGF receptor, GDNF family receptor alpha1, GDNF family receptor alpha2, GDNF family receptor alpha3, GDNF family receptor alpha4, a RET receptor, a LIF receptor, an angiotensin receptor, c-Met, a Frizzled receptor (FZD) and a Smoothened receptor. 
     
     
         5 . The method of  claim 4 , wherein the agent is a chemical compound, an antibody or a peptide comprising between 2 and 400 amino-acid residues. 
     
     
         6 . The method of  claim 5 , wherein the peptide has 95%-100% homology to a polypeptide selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, and SEQ ID NO:27. 
     
     
         7 . The method of  claim 1 , wherein the agent is selected from a group or library containing between 1 and 1 billion chemical compounds. 
     
     
         8 . The method of  claim 1 , wherein the agent is an RNA molecule comprising between 8 and 60 nucleotides 
     
     
         9 . The method of  claim 1 , wherein the agent is selected from the endogenous genes in a human. 
     
     
         10 . The method of  claim 9 , wherein the endogenous gene is artificially modified by gene editing methods.