Methods for treating and/or reversing neurodegenerative diseases and/or disorders

• US 9,540,611 B2
• Filed: 07/28/2011
• Issued: 01/10/2017
• Est. Priority Date: 07/28/2010
• Status: Active Grant

• Current Assignee: Neuralstem Incorporated (City of Tianjin (China))
• Original Assignee: Neuralstem Incorporated (City of Tianjin (China))
• Inventors: Shyu, Woei-Cherng, Lin, Shinn-Zong, Wang, Hsiao-Jung, Johe, Karl K.
• Primary Examiner(s): Weidner, Adam M
• Assistant Examiner(s): Fontainhas, Aurora M
• Application Number:
  US13/192,972
• Publication Number:
  US 20120177612A1
• Time in Patent Office: 1,993 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 5/0623 Stem cells

Abstract

The present disclosure provides methods for the treatment of neurological diseases/disorders using neural stem cells (NSCs) obtained from a spinal cord tissue. The methods may include the use of a NSC population to treat a neurological disease/disorder of the brain. Such methods may include introducing exogenously cultured and expanded NSCs into the brain, which differentiate into neurons capable of integrating in vivo into the brain tissue in a sufficient manner to ameliorate the symptoms associated with the neurological disease/disorder.

Claims

1. A method for inhibiting or relieving a disease or disorder associated with neuronal cell loss in a brain, said method comprising:

a) obtaining at least one stem cell from spinal cord tissue of a human having a gestational age of about 5 to about 20 weeks;

b) expanding the at least one stem cell to form an expanded stem cell population; and

c) injecting a therapeutically effective amount of the expanded stem cell population to at least one area of the brain of a subject.

2. The method of claim 1 wherein the expanded stem cell population differentiates into neurons that engraft in vivo into the brain of the subject.

3. The method of claim 1, wherein the disease or disorder is caused by cerebral ischemia, hemorrhage, and trauma.

4. The method of claim 3, wherein the disease or disorder involves paralysis, speech impairment, loss of memory, or reasoning ability.

5. The method of claim 3, wherein the disease or disorder involves motor dysfunction or cognitive deficit.

6. The method of claim 1, wherein expanding the at least one neural stem cell includes culturing the neural stem cell in absence of serum.

7. The method of claim 1, wherein expanding the at least one stem cell to form an expanded stem cell population is conducted in the absence of LIF.

8. The method of claim 1, wherein expanding the at least one neural stem cell includes exposing the at least one neural stem cell to at least one growth factor.

10. The method of claim 1, wherein at least 30% of the expanded stem cell population is capable of generating neurons in brain tissue of the subject.

11. The method of claim 1, wherein at least 50% of the expanded stem cell population is capable of differentiating into neurons in vitro.

12. The method of claim 1, wherein the at least one area of the brain includes cerebral hemispheres, cerebral cortex, subcortex motor cortex, striatum, internal capsule, thalamus, hypothalamus, hippocampus, midbrain, brainstem, and cerebellum.

13. The method of claim 1, wherein the subject experienced an event that caused cerebral ischemia.

14. The method of claim 13, wherein the event is a stroke.

9. The method of 8, wherein the growth factor is selected from the group consisting of bFGF, EGF, TGF-alpha, aFGF and combinations thereof.

15. A method of inhibiting or relieving stroke in a subject in need thereof, said method comprising:

a) isolating at least one neural stem cell from spinal cord tissue of a human having a gestational age of about 5 to about 20 weeks;

b) expanding in vitro said neural stem cell to form an expanded population;

c) concentrating the expanded population; and

d) introducing a therapeutically effective amount of said expanded population to at least one area of the subject brain.

16. The method of claim 15 wherein at least 20% of the expanded population is capable of generating neurons in brain tissue of the subject.

17. The method of claim 15, wherein expanding the at least one neural stem cell includes culturing the neural stem cell in absence of serum.

18. The method of claim 15, wherein expanding the at least one stem cell to form an expanded stem cell population is conducted in the absence of LIF.

19. The method of claim 15, wherein expanding the at least one neural stem cell includes exposing the at least one neural stem cell to at least one growth factor.

20. The method of claim 19, wherein the growth factor is selected from the group consisting of bFGF, EGF, TGF-alpha, aFGF and combinations thereof.

21. The method of claim 15, wherein at least 30%, of the expanded population is capable of generating neurons in brain tissue of the subject.

22. The method of claim 15, wherein introducing the therapeutically effective amount of the expanded population includes injecting at least a portion of the therapeutically effective amount into one to a plurality of areas of the recipient brain.

23. The method of claim 22, wherein the areas of the recipient brain include cerebral hemispheres, cerebral cortex, subcortex motor cortex, striatum, internal capsule, thalamus, hypothalamus, hippocampus, midbrain, brainstem, and cerebellum.