Transplantation of bone marrow stromal cells for treatment of neurodegenerative diseases

• US 20060275272A1
• Filed: 05/09/2006
• Published: 12/07/2006
• Est. Priority Date: 05/14/1999
• Status: Active Grant

• Current Assignee: Henry Ford Health System
• Original Assignee: Henry Ford Health System
• Inventors: Li, Yi, Chopp, Michael
• Granted Patent: US 8,017,112 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• 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: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• 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

Abstract

The present invention relates to a treatment of an autoimmune demyelinating disease/disorder. Also included in the present invention is the use of bone marrow stromal cells for the treatment of multiple sclerosis (MS).

Claims

1. A method of treating a mammal having an autoimmune demyelinating disease/disorder, the method comprising isolating a stromal cell from a bone marrow sample, and administering said stromal cell to said mammal, wherein the presence of said stromal cell in the CNS of the mammal effects treatment of said disease/disorder, further wherein the presence of said stromal cell in the CNS of the mammal reduces axonal loss.

2. The method of claim 1, wherein said stromal cell is selected from the group consisting of an autologous stromal cell, an allogeneic stromal cell, a syngeneic stromal cell, and a xenogeneic stromal cell, with respect to said mammal.

3. The method of claim 1, wherein said mammal is a human.

4. The method of claim 1, wherein said stromal cell is derived from a human donor.

5. The method of claim 1, wherein said autoimmune demyelinating disease/disorder is selected from the group consisting of a genetic disease, multiple sclerosis (MS), and a neurodegenerative disease.

6. The method of claim 5, wherein said disease/disorder is injury to a tissue of said CNS.

7. The method of claim 5, wherein said disease/disorder is injury to a ell of said CNS.

8. The method of claim 5, wherein said disease/disorder is within the brain of said mammal.

9. The method of claim 1, wherein said stromal cell administered to said CNS remains present or replicates in said CNS.

10. The method of claim 1, wherein said stromal cell administered to said CNS does not result in a cell replacement therapy.

11. The method of claim 1, wherein said stromal cell administered to said CNS induces expression of a growth factor within neighboring cells.

12. The method of claim 11, wherein said neighboring cells are parenchymal cells.

13. The method of claim 11, wherein said stromal cell induces expression of a trophic factor in parenchymal cells, further wherein expression of said trophic factor in parenchymal cells attributes to the reduction of axonal injury and improvement of neurological outcome.

14. The method of claim 1, wherein prior to administering said stromal cell to said mammal, said cell is cultured in vitro for a period of time.

15. The method of claim 1, wherein prior to administering said stromal cell to said mammal, said stromal cell is transfected with an isolated nucleic acid encoding a therapeutic protein, wherein when such protein is secreted by said stromal cell, said protein serves to effect treatment of said disease/disorder.

16. The method of claim 1, wherein said stromal cell is administered to said mammal by a route selected from the group consisting of intravascular, intracerebral, parenteral, intraperitoneal, intravenous, epidural, intraspinal, intrastemal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, and intramuscular.

20. The method of claim 1, wherein said stromal cell present in the CNS activates the proliferation of neighboring cells.

21. The method of claim 1, wherein said stromal cell is administered concomitantly with a growth factor.

22. The method of claim 1, wherein said stromal cell administered to said mammal prevents axonal fiber loss in the cells of the mammal.

23. The method of claim 1, wherein said stromal cell administered to said mammal prevents demyelination in the cells of the mammal.

24. The method of claim 13, wherein said trophic factor is selected from the group consisting of NGF, BDNF, VEGF, and bFGF.

25. The method of claim 1, wherein said stromal cell in the CNS of the mammal induces angiogenesis.

26. The method of claim 1, wherein said stromal cell in the CNS of the mammal induces neurogenesis.

27. The method of claim 1, wherein said stromal cell in the CNS of the mammal induces syaptogenesis.

17. The method of clam 1, wherein said stromal cell is administered to said mammal at the site of injury.

18. The method of clam 1, wherein said stromal cell is administered to said mammal at an adjacent site to the site of injury.

19. The method of claim 18, wherein following administering said stromal cell to said mammal, said stromal cell migrates to the site of injury.