Method of diagnosing adolescent idiopathic scoliosis and related syndromes

Abstract

A method for diagnosing an increased risk for a disease characterized by a dysfunctional melatonin-signaling path-way in an animal comprising detecting the presence or absence of at least one impairment in melatonin-signaling pathway in at least one of the animal's cells, wherein the presence of at least one impairment in melatonin-signaling pathway indicates that the animal possesses an increased risk of developing said disease, and a method of screening for a compound useful in the treatment of a disease characterized by a dysfunctional melatonin-signaling pathway, said method comprising the steps of contacting a candidate compound with at least one cell expressing at least one melatonin-signaling pathway impairment, wherein the candidate compound is selected if said melatoninsignaling pathway impairment is reduced in the presence of the candidate compound as compared to that in the absence thereof.

1 . A method for diagnosing an increased risk for a disease characterized by a dysfunctional melatonin-signaling pathway in an animal comprising detecting the presence or absence of at least one impairment in melatonin-signaling pathway in at least one of the animal's cells, wherein the presence of at least one impairment in melatonin-signaling pathway indicates that the animal possesses an increased risk of developing said disease.  
     
     
         2 . A method as in  claim 1 , wherein said disease characterized by a dysfunctional melatonin-signaling pathway is adolescent idiopathic scoliosis or an other disease involving spinal deformities.  
     
     
         3 . A method as in  claim 1 , wherein said disease characterized by a dysfunctional melatonin-signaling pathway is adolescent idiopathic scoliosis.  
     
     
         4 . A method as in  claim 1 , wherein said impairment is detected by an accumulation of cyclique adenosine 5′-monophosphate (cAMP) in at least one of said cells.  
     
     
         5 . A method as in  claim 4 , wherein said accumulation of cyclique adenosine 5′-monophosphate (cAMP) is induced by a known activator of adenylyl cyclase, and wherein the inhibition of said accumulation by a known melatonin-signaling pathway agonist is detectably reduced in at least one said cells as compared to that obtained in a control cell.  
     
     
         6 . A method as in  claim 5 , wherein said known melatonin-signaling pathway agonist is melatonin or an analog thereof.  
     
     
         7 . A method as in  claim 5 , wherein said known melatonin-signaling pathway agonist is GTP or an analog thereof.  
     
     
         8 . A method as in  claim 5 , wherein said known activator of adenylyl cyclase is forskolin or an analog thereof.  
     
     
         9 . A method as in  claim 1 , wherein said impairment is detected by an absence of proliferation of in at least one of said cells in presence of a known melatonin-signaling pathway agonist.  
     
     
         10 . A method as in  claim 1 , wherein said impairment is detected by a reduction of inhibition of osteoclasts resorption activity by the known melatonin-signaling pathway agonist, and wherein the candidate compound is selected if said reduction of inhibition of osteoclasts resorption activity is inhibited in the presence of the candidate compound as compared to that in the absence thereof.  
     
     
         11 . A method as in  claim 1 , wherein said cells are selected from the group consisting of osteoblasts, osteoclasts, lymphocytes, monocytes and myoblasts.  
     
     
         12 . A method as in  claim 1 , wherein said cells are blood cells.  
     
     
         13 . A method as in  claim 1 , wherein said cells are lymphocytes.  
     
     
         14 . A method of screening for a compound useful in the treatment of a disease characterized by a dysfunctional melatonin-signaling pathway, said method comprising the steps of 
 contacting a candidate compound with at least one cell expressing at least one melatonin-signaling pathway impairment in the presence of a known melatonin-signaling pathway agonist,    wherein the candidate compound is selected if said melatonin-signaling pathway impairment is reduced in the presence of the candidate compound as compared to that in the absence thereof.    
     
     
         15 . A method as in  claim 14 , wherein said disease characterized by a dysfunctional melatonin-signaling pathway is adolescent idiopathic scoliosis or an other disease involving spinal deformities.  
     
     
         16 . A method as in  claim 14 , wherein said disease characterized by a dysfunctional melatonin-signaling pathway is adolescent idiopathic scoliosis.  
     
     
         17 . A method as in  claim 14 , wherein said impairment is detected by an accumulation of cyclique adenosine 5′-monophosphate (cAMP) in said cell as compared to that in a control cell.  
     
     
         18 . A method as in  claim 16 , further comprising the step of articicially inducing said accumulation of cyclique adenosine 5′-monophosphate (cAMP) by a known activator of adenylyl cyclase.  
     
     
         19 . A method as in  claim 14 , wherein said known melatonin-signaling pathway agonist is melatonin or an analog thereof.  
     
     
         20 . A method as in  claim 14 , wherein said known melatonin-signaling pathway agonist is GTP or an analog thereof.  
     
     
         21 . A method as in  claim 18 , wherein said known activator of adenylyl cyclase is forskolin or an analog thereof.  
     
     
         22 . A method as in  claim 14 , wherein said impairment is detected by an absence of said cells proliferation in presence of the known melatonin-signaling pathway agonist.  
     
     
         23 . A method as in  claim 14 , wherein said impairment is detected by a reduction of inhibition of osteoclasts resorption activity by the known melatonin-signaling pathway agonist, and wherein the candidate compound is selected if said reduction of inhibition of osteoclasts resorption activity is inhibited in the presence of the candidate compound as compared to that in the absence thereof.  
     
     
         24 . A method as in  claim 14 , wherein said cells are selected from the group consisting of osteoblasts, osteoclasts, lymphocytes, monocytes and myoblasts.  
     
     
         25 . A method as in  claim 14 , wherein said cells are blood cells.  
     
     
         26 . A method as in  claim 14 , wherein said cells are lymphocytes.