METHOD AND COMPOSITION FOR MODULATING CANONICAL WNT PATHWAY USING FOLATE AND INOSITOL
The canonical Wnt signaling pathway is implicated in many disorders including neural tube defects, limb malformations, and heart defects, developmental disorders associated with alcohol exposure (fetal alcohol syndrome) or exposure to bipolar medications (i.e. lithium), wound healing, and Alzheimer's disease. Elevated plasma homocysteine (HCy), which results from folate (folic acid, FA) deficiency, the mood-stabilizing drug lithium (Li), and alcohol (ethanol) are linked to the induction of human congenital heart and neural tube defects. FA supplementation ameliorates the observed developmental errors in the Li-HCy, or alcohol-exposed mouse embryos and normalized heart function. Li, HCy or Wnt3A suppress Wnt-modulated Hex and Islet-1 expression. FA protects from the gene misexpression that is induced by all three factors. Administration of myo-inositol with FA synergistically enhances the protective effect.
1 . A method of treating a disorder caused by altered canonical Wnt signaling in a patient in need thereof comprising the step of administering a therapeutically effective combination of a folate compound and an inositol compound.
2 . The method of claim 1 wherein the altered canonical Wnt signaling is caused by elevated homocysteine levels.
3 . The method of claim 1 wherein the altered canonical Wnt signaling is caused by exposure to a compound selected from the group consisting of lithium and alcohol.
4 . The method of claim 1 , wherein the disorder is selected from the group consisting of developmental disorders including neural tube defects, limb malformations, and heart defects, developmental disorders associated with alcohol exposure (fetal alcohol syndrome) or exposure to bipolar medications (i.e. lithium), stem cell development and proliferation, wound healing, cancer, Alzheimer's disease, diabetes and osteoporosis.
5 . The method of claim 1 , wherein the disorder is selected from the group consisting of developmental disorders including neural tube defects and heart defects, developmental disorders associated with alcohol exposure (fetal alcohol syndrome) or exposure to bipolar medications (i.e. lithium), and wound healing.
6 . The method of claim 1 wherein the folate compound is folic acid.
7 . The method of claim 1 wherein the inositol compound is myo-inositol.
8 . A method of modulating canonical Wnt signaling comprising the step of contacting a target cell population with a therapeutically effective combination of a folate compound and an inositol compound.
9 . The method of claim 8 wherein the folate compound is folic acid.
10 . The method of claim 8 wherein the inositol compound is myo-inositol.
11 . A method of preventing the formation of a disorder caused by altered canonical Wnt signaling in a patient at risk therefrom comprising the step of administering a therapeutically effective combination of a folate compound and an inositol compound.
12 . The method of claim 11 , wherein the disorder caused by altered canonical Wnt signaling is selected from the group consisting of developmental disorders including neural tube defects, limb malformations and heart defects, developmental disorders associated with alcohol exposure (fetal alcohol syndrome) or exposure to bipolar medications (i.e. lithium), stem cell development and proliferation, wound healing, cancer, Alzheimer's disease, diabetes and osteoporosis.
13 . The method of claim 11 wherein the disorder caused by altered canonical Wnt signaling is selected from the group consisting of developmental disorders including neural tube defects and heart defects, developmental disorders associated with alcohol exposure (fetal alcohol syndrome) or exposure to bipolar medications (i.e. lithium) and wound healing.
14 . The method of claim 11 wherein the altered canonical Wnt signaling is caused by elevated homocysteine levels.
15 . The method of claim 11 wherein the altered canonical Wnt signaling is caused by the exposure to a compound selected from the group consisting of lithium and alcohol.
16 . The method of claim 11 wherein the inositol compound is myo-inositol.
17 . The method of claim 11 wherein the folate compound is folic acid.
18 . A composition comprising:
a therapeutically effective amount of a folate compound;
a therapeutically effective amount of an inositol compound; and
a pharmaceutically acceptable carrier.
19 . The composition of claim 18 wherein the folate compound is folic acid.
20 . The composition of claim 18 wherein the inositol compound is myo-inositol.