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).
Abstract:
A method of classifying a subject having idiopathic scoliosis (IS) or at risk of developing IS comprising: determining the cellular response to Gi stimulation in a cell sample from the subject in the presence of OPN; determining the cellular response to Gi stimulation in a cell sample from the subject in the absence of OPN; and comparing the cellular response obtained in the presence of OPN with the cellular response obtained in the absence of OPN, whereby the comparing step enables the classification of the subject into one IS functional group. Also provided is the use of the foregoing method to classify borderline subjects and kits for applying the methods.
Abstract:
A method for the prevention or treatment of scoliosis in a human subject comprising: (a)(i) measuring osteopontin (OPN) protein expression in a biological fluid sample from the subject over time; or (ii) measuring osteopontin (OPN) protein expression in a biological fluid sample from the subject and comparing the OPN protein expression to an OPN protein expression in a control biological fluid sample; (b) identifying the subject as being at risk of developing scoliosis when OPN protein expression increases in the subject sample over time; or when OPN protein expression is higher in the subject sample than that in the control sample; and (c) reducing OPN protein levels in the subject identified as being at risk of developing a scoliosis, thereby aiding in the prevention or treatment of scoliosis.
Abstract:
Methods of stratifying a subject having or at risk for developing adolescent idiopathic scoliosis (AIS) into diagnostically or clinically useful subclasses are provided. The stratification is based on the subject's PTPμ expression and/or activity and/or PIPK1γ expression and/or activity. Also provided are methods of predicting the risk of developing a scoliosis also based on the subject's PTPμ expression and/or activity and/or PIPK1γ expression and/or activity; and methods of increasing GiPCR signaling in cells of a subject in need thereof comprising administering to the subject's cells an effective amount of an inhibitor of PIPK1γ tyrosine phosphorylation; an activator of PIPK1Y tyrosine dephosphorylation; and/or an inhibitor of PIPK1γ expression and/or activity.
Abstract:
A composition for classifying a human pediatric subject having adolescent idiopathic scoliosis (AIS), comprising (a) a cell sample of the subject; and (b) a known melatonin-signaling pathway agonist, wherein said melatonin signaling pathway in said cell sample has been artificially induced by said melatonin-signaling pathway agonist, wherein the cell sample is selected from the group consisting of blood cell sample, osteoblast cell sample, osteoclast cell sample and myoblast cell sample, and whereby the composition enables the detection of the presence or absence of at least one impairment in the melatonin-signaling pathway in cells from said cell sample and thereby enables the classification of subject.
Abstract:
The present invention provides a method of predicting brace treatment outcome in a subject in need thereof comprising i) classifying the subject into functional group FG1, FG2 or FG3, wherein the classification enables the prediction of brace treatment outcome. Also provided are methods of determining risk of developing scoliosis, methods of treating Idiopathic scoliosis and kits for applying the methods.
Abstract:
Methods of stratifying a subject having or at risk for developing adolescent idiopathic scoliosis (AIS) into diagnostically or clinically useful subclasses are provided. The stratification is based on the subject's Giα protein serine phosphorylation profile and/or the degree of imbalance in G-protein coupled receptor responses to Giα and Gsα protein stimulation. In some embodiments, the methods involve detecting or determining the level of serine phosphorylated Giα1 and/or Giα3 proteins in the cell sample, and/or determining a ratio between the response to Giα protein stimulation and the response to Gsα protein stimulation from a biological sample from the subject. Methods for predicting the risk of an AIS subject for developing a severe scoliosis, for predicting the subject's responsiveness to bracing treatment, and for identifying therapeutically useful compounds are also provided, as well as kits therefor.
Abstract:
Disclosed herein are novel molecular markers associated with idiopathic scoliosis (IS). Accordingly, the present invention concerns novel methods of identifying subjects at risk of developing IS or suffering from IS and of genotyping and classifying IS subjects into genetic and functional groups. Also provided are compositions, DNA chips and kits for applying the methods.
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).
Abstract:
A method for preventing or reducing the risk of perinatal or neonatal morbidity and mortality caused by antenatal inflammation in humans is described. This method is based on the administration of a compound of formula I or a pharmaceutically acceptable salt thereof to an expectant human mother suffering from antenatal fetal inflammation. The method prevents or reduces the risk of organ damages, including brain, lung and intestinal damages, and sequelae therefrom, in the neonates, as well as the risk of neonatal death.