Methods of treating or inhibiting onset of Huntington's disease
View Patent ↗The disclosure herein relates generally to a method of treating or inhibiting onset of Huntington's disease. This method involves selecting a subject having or at risk of having Huntington's disease and administering to the subject one or modulators of one or more genes as described herein, or proteins encoded therefrom, under conditions effective to treat or inhibit onset of Huntington's disease in the subject.
1. A method of treating or inhibiting onset of Huntington's disease, said method comprising:
selecting a subject having or at risk of having hypomyelination; and
administering to the selected subject one or more modulators of a gene or protein encoded thereof involved in the NKX2.2→OLIG2→SOX10→MYRF regulatory cascade, wherein the method results in an increase in myelination in the subject.
2. The method of claim 1 , wherein the gene or protein encoded therefrom is selected from the group consisting of a SOX10 gene or protein encoded therefrom, a MYRF gene or protein encoded therefore, an OLIG2 gene or protein encoded therefrom, a TCF7L2 gene or protein encoded therefrom, and a NKX2.2 gene or protein encoded therefrom, or any combination thereof.
3. The method of claim 1 , wherein said administering is carried out using intracerebral delivery, intrathecal delivery, intranasal delivery, or via direct infusion into brain ventricles.
4. The method of claim 1 , further comprising:
administering to the selected subject a preparation of human glial progenitor cells.
5. The method of claim 4 , wherein the preparation of glial progenitor cells are astrocyte-biased glial progenitor cells.
6. The method of claim 4 , wherein glial progenitor cells of the preparation are A2B5 + , CD140a + , and/or CD44 + .
7. The method of claim 4 , wherein said preparation of glial progenitor cells is administered to the striatum, forebrain, brain stem, and/or cerebellum of the subject.
8. The method of claim 1 , wherein the subject is human.
9. The method of claim 1 , wherein the modulator upregulates expression of said gene or protein encoded therefrom.
10. The method of claim 1 , wherein the modulator is selected from the group consisting of:
a) a nucleic acid molecule;
b) a peptide; and
c) a small molecule.
11. The method of claim 10 , wherein the modulator is a nucleic acid molecule comprising a nucleotide sequence encoding a protein involved in the NKX2.2→OLIG2→SOX10→MYRF regulatory cascade.
12. The method of claim 11 , wherein said protein encoded by the nucleic acid molecule is selected from the group consisting of:
a) a SOX10 protein;
b) a MYRF protein; and
c) any combination thereof.
13. The method of claim 11 , wherein the nucleic acid molecule comprises an expression vector.
14. The method of claim 13 , wherein the expression vector is a viral vector selected from the group consisting of an adenovirus vector, adeno-associated virus vector, retrovirus vector, lentivirus vector, and herpes virus vector.
15. The method of claim 13 , wherein the expression vector is a plasmid.
16. The method of claim 11 , wherein the nucleotide sequence encoding the protein is operably linked to a promoter.
17. The method of claim 16 , wherein the promoter is an inducible promoter.
18. The method of claim 4 , wherein the human glial progenitor cells are genetically modified to express a gene or protein encoded thereof that is involved in the NKX2.2→OLIG2→SOX10→MYRF regulatory cascade.
19. The method of claim 17 , wherein the gene or protein encoded thereof is selected from the group consisting of:
a) a SOX10 gene or protein encoded therefrom;
b) a MYRF gene or protein encoded therefrom; and
c) any combination thereof.