Method of treating and prognosing scoliotic patient subgroups

Abstract

The present invention provides a method of treating a subject in need thereof comprising classifying the subject into functional group FG1, FG2 or FG3, wherein i) when the subject is classified into the FG1 functional group, (A) the level of OPN or the activity of OPN in said subject is increased; (B) the subject is not treated with a brace; or (C) a combination of (A) and (B); and ii) when the subject is classified into the FG2 or FG3 functional group, (A) the level of OPN or the activity of OPN in said subject is decreased; (B) the subject is treated with a brace; or (C) a combination of (A) and (B).

1 . A method of treating a subject in need thereof comprising classifying the subject into functional group FG1, FG2 or FG3, wherein
 i) when the subject is classified into the FG1 functional group, (A) the level of OPN or the activity of OPN in said subject is increased; (B) the subject is not treated with a brace; or (C) a combination of (A) and (B); and   ii) when the subject is classified into the FG2 or FG3 functional group, (A) the level of OPN or the activity of OPN in said subject is decreased; (B) the subject is treated with a brace; or (C) a combination of (A) and (B).   
     
     
         2 . The method of  claim 1 , wherein i) comprises treating said subject with:
 (a) OPN;   (b) an OPN agonist;   (c) a treatment or preventive measure which increases the level of circulating OPN;   (d) an inhibitor of CD44 expression or activity; or   (e) a combination of at least two of (a) to (d); and   and wherein ii) comprises treating said subject with:   (f) an OPN antagonist;   (g) a treatment or preventive measure which decreases the level of circulating OPN;   (h) an inhibitor of integrin expression or activity;   (i) sCD44 or a stimulator of CD44 expression; or   (j) a combination of at least two of (f) to (i).   
     
     
         3 . The method of  claim 2 , wherein the method comprises treating said subject with (b) the OPN agonist and wherein the OPN agonist is (b i) HA; (b ii) an OPN functional fragment; (b iii) an OPN functional derivative; or (b iv) a combination of at least two of (b i) to (b iii). 
     
     
         4 . The method of  claim 2 , wherein the method comprises treating said subject with (c) the treatment or preventive measure which increases the level of circulating OPN and wherein the treatment or preventive measure which increases the level of circulating OPN comprises applying pulsative compressive pressure for 15-90 minutes on at least one body part of said subject. 
     
     
         5 . The method of  claim 4 , wherein the treatment or preventive measure which increases the level of circulating OPN comprises applying low intensity pulse ultrasound (LIPUS). 
     
     
         6 . The method of  claim 2 , wherein the method comprises treating said subject with (d) the inhibitor of CD44 expression or activity and wherein the inhibitor of CD44 expression or activity is an antibody which binds to CD44 or a siRNA or antisense specific for CD44. 
     
     
         7 . The method of  claim 2 , wherein the method comprises treating said subject with (e) the OPN antagonist and wherein the OPN antagonist is (f i) melatonin; (f ii) selenium; (f iii) an antibody which binds to OPN; (f iv) an siRNA or antisense specific for OPN; (f v) a molecule that blocks the binding of OPN to integrins preferably a RGD peptide or derivative thereof or a peptide fragment of OPN comprising a RGD motif; or (f vi) a combination of at least two of (f i) to (f vi). 
     
     
         8 . The method of  claim 2 , wherein the method comprises treating said subject with (g) the treatment or preventive measure which decreases the level of circulating OPN and wherein the treatment or preventive measure which decreases the level of circulating OPN is: (g i) brace treatment; (g ii) accupoint heat sensitive moxibustion; (g iii) heat therapy with pad; (g iv) electroacupuncture; (g v) thermal bath; or (g vi) a combination of at least two of (g i) to (g v). 
     
     
         9 . The method of  claim 2 , wherein the method comprises treating said subject with (h) the inhibitor of integrin activity and wherein the inhibitor of integrin activity is (h i) an antibody that binds specifically to integrin subunit α 5 ; (h ii) an antibody that binds specifically to integrin subunit β 1 ; (h iii) an antibody that binds specifically to integrin subunit β 3 ; (h iv) an antibody that binds specifically to integrin subunit β 5 ; (h v) an antibody that binds specifically to integrin subunits α 5 β 1 ; or (h vi) a combination of at least two of (h i) to (h v). 
     
     
         10 . The method of  claim 9 , wherein the inhibitor of integrin activity is Volociximab™; ATN-161, Etaratuzumab™, Etaracizzumab™, Vitaxin™, MEDI-522, CNT095 or Cilengitide™. 
     
     
         11 . The method of  claim 9 , wherein the inhibitor of integrin activity is Volociximab™ or Cilengitide™. 
     
     
         12 . The method of  claim 9 , wherein the integrin is α 5 β 1 . 
     
     
         13 . The method of  claim 2 , wherein the method comprises treating said subject with (h) the inhibitor of integrin expression and wherein the inhibitor of integrin expression is (h i) an siRNA or antisense specific to integrin subunit α5; (h ii) an siRNA or antisense specific to integrin subunit β1; (h iii) an siRNA or antisense specific to integrin subunit β3; (h iv) an siRNA or antisense specific to integrin subunit β5; (v) a combination of at least two of (h i) to (h vi). 
     
     
         14 . The method of  claim 9 , comprising treating the FG2 or FG3 subject with a brace. 
     
     
         15 . The method of  claim 14 , further comprising measuring the level of OPN in a blood sample from the subject periodically. 
     
     
         16 . The method of  claim 15 , wherein the level of OPN is measured once a month. 
     
     
         17 . The method of  claim 1 , wherein the subject is a pediatric subject. 
     
     
         18 . The method of  claim 1 , wherein classifying the subject comprises (i) determining changes in cellular impedance following Gi-stimulation; (ii) measuring changes in cAMP concentration following Gi-stimulation; (iii) determining the phosphorylation pattern of Giα proteins; (iv) determining cellular proliferation in a cell sample from the subject. 
     
     
         19 . The method of  claim 18 , wherein the cellular impedance is measured by cellular dielectric spectroscopy (CDS). 
     
     
         20 . The method of  claim 1 , wherein the subject is a subject diagnosed with adolescent idiopathic scoliosis (AIS).