Non-human mammal model of human degenerative disorder, uses thereof, and method of treating human degenerative disorder
The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.
1. A method of treating Huntington's disease in a human subject, said method comprising:
selecting a human subject having Huntington's disease;
providing a preparation of human cells comprising glial progenitor cells, wherein said glial progenitor cells of the preparation endogenously co-express CD44 and CD140a; and
administering, to the selected subject, the provided preparation of human cells comprising glial progenitor cells at a dosage effective to treat Huntington's disease in the subject.
2. The method of claim 1 , wherein at least 80% of the cells in the preparation are glial progenitor cells co-expressing CD44 and CD140a.
3. The method of claim 1 , wherein at least 90% of the cells in the preparation are glial progenitor cells co-expressing CD44 and CD140a.
4. The method of claim 1 , wherein said preparation of human cells is administered to the striatum, forebrain, brain stem, and/or cerebellum of the subj ect.
5. The method of claim 1 , wherein the preparation of human cells comprising glial progenitor cells is derived from fetal tissue, embryonic stem cells, or induced pluripotent stem cells.
6. The method of claim 1 further comprising:
inducing addition of medium spiny neurons in conjunction with said administering of the preparation of human cells.
7. The method of claim 6 , wherein said inducing comprises administering one or more reagents selected from the group consisting of brain- derived neurotrophic factor, noggin, neurotrophin-4 (“NT-4”), insulin-like growth factor-1, and a combination thereof.
8. The method of claim 1 , wherein said administering is carried out using a cannula.
9. The method of claim 1 further comprising:
administering one or more immunosuppressant agents to the subject in conjunction with said administering the preparation of human cells.
10. The method of claim 9 , wherein the one or more immunosuppressant agents is selected from the group consisting of azathioprine, azathioprine sodium, cyclosporine, daltroban, gusperimus trihydrochloride, sirolimus, and tacrolimus.
11. The method of claim 10 , wherein said immunosuppressant agent is tacrolimus.
12. The method of claim 1 , wherein said effective dose of the preparation comprises 10 5 -10 8 cells.
13. The method of claim 1 , wherein said effective dose of the preparation comprises 10 7 -10 8 cells.
14. A method of treating Huntington's disease in a human subject, said method comprising:
selecting a human subject having Huntington's disease;
providing a preparation of human cells comprising astrocyte-biased glial progenitor cells, wherein said astrocyte-biased glial progenitor cells of the preparation endogenously co-express CD44 and A2B5; and
administering, to the selected subject, the provided preparation of human cells comprising astrocyte-biased glial progenitor cells at a dosage effective to treat Huntington's disease in the subject.
15. The method of claim 14 , wherein at least 80% of the cells in the preparation are astrocyte-biased glial progenitor cells co-expressing CD44 and A2B5.
16. The method of claim 14 , wherein at least 90% of the cells in the preparation are astrocyte-biased glial progenitor cells co-expressing CD44 and A2B5.
17. The method of claim 14 , wherein said preparation of human cells is administered to the striatum, forebrain, brain stem, and/or cerebellum of the subject.
18. The method of claim 14 further comprising:
inducing addition of medium spiny neurons in conjunction with said administering of the preparation of human cells.
19. The method of claim 14 , wherein the preparation of human cells comprising astrocyte-biased glial progenitor cells is derived from fetal tissue, embryonic stem cells, or induced pluripotent stem cells.
20. The method of claim 14 , wherein said administering is carried out using a cannula.
21. The method of claim 14 further comprising:
administering one or more immunosuppressant agents to the subject in conjunction with said administering the preparation of human cells.
22. The method of claim 14 , wherein said effective dose of the preparation comprises 10 5 -10 8 cells.
23. The method of claim 14 , wherein said effective dose of the preparation comprises 10 7 -10 8 cells.