Method of determining the risk of scoliosis

Abstract

A method for determining the risk for developing a scoliosis comprising monitoring osteopontin (OPN) expression in a sample from a subject over time; wherein an OPN expression that increases in the subject sample over time is indicative that the subject is at risk for developing a scoliosis.

1 . A method for determining the risk for developing a scoliosis comprising
 (a) monitoring osteopontin (OPN) expression in a sample from a subject over time; or   (b) measuring osteopontin (OPN) expression in a sample from a subject;   
       wherein an OPN expression that increases in the subject sample over time or wherein an OPN expression that is higher in the subject sample than that in a control sample, is indicative that the subject is at risk for developing a scoliosis. 
     
     
         2 . The method of  claim 1 , wherein the monitoring begins when the subject is about three years old. 
     
     
         3 . The method of  claim 1 , wherein the monitoring is performed by measuring OPN expression at a frequency of at least about once per month. 
     
     
         4 . The method of  claim 1 , wherein the monitoring is performed by measuring OPN expression at a frequency of at least about once per six month. 
     
     
         5 . The method of  claim 1 , wherein the monitoring OPN expression is performed using an enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the subject is a likely candidate for developing a scoliosis. 
     
     
         8 . The method of  claim 1 , wherein the subject is a likely candidate for developing adolescent idiopathic scoliosis. 
     
     
         9 . The method of  claim 1 , wherein the subject is pre-diagnosed as having a scoliosis. 
     
     
         10 . The method of  claim 1 , wherein the subject is pre-diagnosed with adolescent idiopathic scoliosis. 
     
     
         11 . A method of stratifying a subject having a scoliosis comprising
 measuring osteopontin (OPN) expression in a sample from the subject;   whereby the measuring step enables the stratification of the subject into a scoliosis subgroup.   
     
     
         12 . A method for assessing the efficacy of a brace on a subject having a scoliosis comprising
 measuring osteopontin (OPN) expression in a sample from the subject prior to and at least once after bracing the subject,   wherein an increase in the OPN expression after as compared to prior to bracing the subject is indicative that the brace is ineffective.   
     
     
         13 . The method of  claim 12 , wherein the determining the OPN expression after the bracing is performed at least one month after the bracing. 
     
     
         14 . The method of  claim 12 , wherein the determining the OPN expression after bracing the subject is performed at least two months hours after the bracing. 
     
     
         15 . The method of  claim 12 , wherein the determining the OPN expression after bracing the subject is performed at least three months after the bracing. 
     
     
         16 . The method of  claim 12 , wherein the determining the OPN expression after bracing the subject is performed at least six months after the bracing. 
     
     
         17 . The method of  claim 1 , wherein the method further comprises measuring soluble CD44 receptor (sCD44) expression in the sample from the subject. 
     
     
         18 . The method of  claim 1 , wherein the sample from the subject is a biological fluid from the subject. 
     
     
         19 . The method of  claim 18 , wherein the biological fluid is selected from the group consisting of blood, urine, tear and saliva. 
     
     
         20 . The method of  claim 19 , wherein the biological fluid is plasma. 
     
     
         21 . The method of  claim 1 , wherein the OPN expression is OPN protein. 
     
     
         22 . The method of  claim 21 , wherein the determining of the OPN expression is performed with an antibody that specifically binds to OPN. 
     
     
         23 . The method of  claim 22 , wherein the measuring OPN expression is performed using an enzyme-linked immunosorbent assay (ELISA). 
     
     
         24 . The method of  claim 23 , wherein the sample is a plasma sample and an OPN expression that is higher than 700 nanograms per milliliter of plasma is indicative that the subject is at risk for developing a scoliosis. 
     
     
         25 . The method of  claim 23 , wherein the sample is a plasma sample and an OPN expression that is higher than 800 nanograms per milliliter of plasma is indicative that the subject is at risk for developing a scoliosis. 
     
     
         26 . The method of  claim 1 , wherein the OPN expression is OPN RNA. 
     
     
         27 . The method of  claim 1 , wherein the sample from the subject is a paraspinal muscle biopsy and the OPN expression is OPN RNA. 
     
     
         28 . A method of selecting an agent as a potential candidate for the reduction or prevention of scoliosis comprising: (a) contacting a candidate agent with a cell expressing osteopontin (OPN), and detecting the expression of OPN, wherein when the expression of OPN is lower in the presence of the candidate agent as compared to in the absence thereof, the candidate agent is selected; (b) contacting a candidate agent with a cell expressing sCD44, and detecting the expression of sCD44, wherein when the expression of sCD44 is higher in the presence of the candidate agent as compared to in the absence thereof, the candidate agent is selected; or (c) administering a candidate agent to a scoliosis model animal before scoliosis has developed in the animal, whereby the candidate is selected when the scoliosis is prevented or reduced in the model animal as compared to in a control animal who was not administered the candidate agent. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein the cell is a cell derived from a scoliotic patient. 
     
     
         31 . (canceled) 
     
     
         32 . A method of preventing or reducing scoliosis comprising administering to a subject having scoliosis a therapeutically effective amount of (a) an osteopontin inhibitor (OPN) or a selenium rich diet; (b) a CD44 inhibitor; or (c) a sCD44 stimulator, whereby scoliosis is thereby prevented or treated. 
     
     
         33 - 34 . (canceled) 
     
     
         35 . The method of  claim 1  wherein the subject is human. 
     
     
         36 . The method of  claim 1  wherein the subject is human female. 
     
     
         37 . The method of  claim 1  wherein the subject is human male. 
     
     
         38 - 47 . (canceled) 
     
     
         48 . A kit for predicting the risk of developing a scoliosis comprising a ligand specific to osteopontin (OPN) and instructions to use the kit for predicting the risk of developing a scoliosis. 
     
     
         49 . The kit of  claim 48 , further comprising a ligand specific to soluble CD44 (sCD44).