MAPC TREATMENT OF BRAIN INJURIES AND DISEASES

• US 20100310570A1
• Filed: 01/23/2007
• Published: 12/09/2010
• Est. Priority Date: 11/09/2005
• Status: Active Grant

• Current Assignee: Athersys, Inc., Augusta University Research Institute, Inc.
• Original Assignee: Athersys, Inc.
• Inventors: Mays, Robert, Hess, David C., Borlongan, Cesar V., Carroll, James E., Deans, Robert J.
• Granted Patent: US 10,117,900 B2
• Time in Patent Office: Days
• US Class Current: 424/141.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4353 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

The invention relates to the treatment of various injuries, disorders, dysfunctions, diseases, and the like of the brain with MAPCs, particularly in some aspects, to the treatment of the same resulting from hypoxia, including that caused by systemic hypoxia and that caused by insufficient blood supply. In some further particulars the invention relates, for example, to the treatment of hypoxic ischemic brain injury with MAPCs, in children for example, and to the treatment of cortical infarcts and stroke with MAPCs in adults, for example.

Claims

1. A method of treating a brain injury in a subject, comprising:

administering to a subject likely to suffer, suffering, or who has suffered a brain injury by an effective route and in an effective amount to treat said brain injury cells that;

are not embryonic stem cells, embryonic germ cells, or germ cells, and can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages.

2. A method according to claim 1, wherein said subject is not treated with an immunosuppressive therapy adjunctively to treatment with said cells.

3. A method according to claim 2, wherein the brain injury is caused by hypoxia.

4. A method according to claim 3, wherein the brain injury is hypoxic ischemic brain injury.

5. A method according to claim 2, wherein the brain injury is caused by an occlusion or a blockage of blood supply.

6. A method according to claim 2, wherein the brain injury is a cortical infarction.

7. A method according to claim 2, wherein the brain injury is a stroke.

8. A method according to claim 2, wherein said cells can differentiate into at least one cell type of each of the endodermal, ectodermal, and mesodermal embryonic lineages.

9. A method according to claim 2, wherein said cells express telomerase.

10. A method according to claim 2, wherein said cells are positive for oct-3/4.

11. A method according to claim 2, wherein said cells have undergone at least 10 to 40 cell doublings in culture prior to their administration to the subject.

12. A method according to claim 2, wherein said cells are mammalian cells.

13. A method according to claim 2, wherein said cells are human cells.

14. A method according to claim 2, wherein said cells are derived from cells isolated from any of placental tissue, umbilical cord tissue, umbilical cord blood, bone marrow, blood, spleen tissue, thymus tissue, spinal cord tissue, adipose tissue, and liver tissue.

15. A method according to claim 2, wherein said cells are allogeneic to the subject.

16. A method according to claim 2, wherein said cells are xenogeneic to the subject.

17. A method according to claim 2, wherein said cells are autologous to the subject.

18. A method according to claim 2, wherein the subject is a human.

19. A method according to claim 2, wherein said cells are administered to said subject in one or more doses comprising 10⁵ to 10⁸ of said cells per kilogram of the subject'"'"'s mass.

20. A method according to claim 19, wherein said cells are administered to the subject in one or more doses comprising 10⁶ to 5×

10⁷ of said cells per kilogram of the subject'"'"'s mass.

21. A method according to claim 2, wherein in addition to said cells, one or more growth factors, differentiation factors, signaling factors, and/or factors that increase homing are administered to said subject.

22. A method according to claim 2, wherein further any combination of one or more of each of the following is administered to said subject:

an antibiotic agent, an anti-fungal agent, and/or an anti-viral agent.

23. A method according to claim 2, wherein said cells are administered in a formulation comprising one or more other pharmaceutically active agents.

24. A method according to claim 23, wherein said formulation further comprises any combination of one or more of:

an antibiotic agent, an anti-fungal agent, and/or an anti-viral agent.

25. A method according to claim 2, wherein said cells are administered to the subject by a parenteral route.

26. A method according to claim 25, wherein said cells are administered by intravenous infusion.

27. A method according to claim 2, wherein said cells are administered to the subject by stereotactic injection.

28. A method according to claim 1, wherein in addition to treatment with said cells, the subject has been, will be, or is being treated with one or more immunosuppressive agents.

29. A method according to claim 1, wherein in addition to treatment with said cells, the subject has been, will be, or is being treated with one or more of a corticosteroid, cyclosporin A, a cyclosporin-like immunosuppressive agent, cyclophosphamide, antithymocyte globulin, azathioprine, rapamycin, FK-506, and a macrolide-like immunosuppressive agent other than FK-506, and an immunosuppressive monoclonal antibody agent.