Pregnancy-induced oligodendrocyte precursor cell proliferation regulated by prolactin

• US 7,534,765 B2
• Filed: 09/27/2006
• Issued: 05/19/2009
• Est. Priority Date: 09/27/2005
• Status: Expired due to Fees

• Current Assignee: Stem Cell Therapeutics Corp. (Pfizer Inc.)
• Original Assignee: Stem Cell Therapeutics Corp. (Pfizer Inc.)
• Inventors: Weiss, Samuel, Gregg, Christopher
• Primary Examiner(s): Romeo; David S
• Assistant Examiner(s): Gamett; Daniel C
• Application Number:
  US11/535,898
• Publication Number:
  US 20070098698A1
• Time in Patent Office: 965 Days
• Field of Search: None
• US Class Current: 514/1.1
• 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 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• 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 38/2257 Prolactin
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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

Abstract

The present invention relates to a method to increase oligodendrocytes and oligodendrocyte precursor cells through administration of prolactin or a prolactin inducing agent.

Claims

1. A method for enhancing the formation of oligodendrocytes endogenously in a mammal, comprising:

selecting a mammal with or suspected of having a disease or condition associated with demyelination; and

enhancing the formation of oligodendrocytes by administering an effective amount of a prolactin to said mammal.

2. The method of claim 1, wherein said disease or condition associated with demyelination is selected from the group consisting of multiple sclerosis, acute disseminated encephalomyelitis, diffuse cerebral sclerosis, necrotizing hemorrhagic encephalitis, leukodystrophies, stroke, spinal cord injury, schizophrenia, bipolar disorder, acute brain injury, and dementia.

3. The method of claim 2, wherein said disease or condition is multiple sclerosis.

4. The method of claim 1, further comprising administration of at least one biological agent selected from the group consisting of epidermal growth factor (EGF), pituitary adenylate cyclase-activating polypeptide (PACAP), fibroblast growth factor (FGF), transforming growth factor alpha (TGFα

), ciliary neurotrophic factor (CNTF), Leukemia Inhibitory Factor (LIF), platelet-derived growth factor (PDGF), estrogen, ovarian hormone, human chorionic gonadotrophin (hCG), and insulin-like growth factor-1.

5. The method of claim 1, wherein said prolactin is administered systemically, subcutaneously, or into the brain.

6. A method of delivering oligodendrocytes to a mammal, comprising:

(a) introducing at least one neural stem cell and/or oligodendrocyte precursor cell into said mammal; and

(b) administering an effective amount of a prolactin or prolactin releasing peptide to said mammal;

under conditions that result in oligodendrocyte formation from said neural stem cell and/or oligodendrocyte precursor cell.

7. The method of claim 6 , further comprising contacting said neural stem cells and/or oligodendrocyte precursor cells with at least one biological agent selected from the group consisting of epidermal growth factor (EGF), pituitary adenylate cyclase-activating polypeptide (PACAP), fibroblast growth factor (FGF), transforming growth factor alpha (TGFα

), ciliary neurotrophic factor (CNTF), Leukemia Inhibitory Factor (LIF), platelet-derived growth factor (PDGF), estrogen, ovarian hormone, human chorionic gonadotrophin (hCG), and insulin-like growth factor-1.

8. The method of claim 7, wherein said biological agent is used before said introduction of said neural stem cell and/or oligodendrocyte precursor cell into said mammal.

9. The method of claim 7, wherein said biological agent is used after said introduction of said neural stem cell and/or oligodendrocyte precursor cell into said mammal.

10. The method of claim 7, wherein said biological agent is used both before and after said introduction of said neural stem cell and/or oligodendrocyte precursor cell into said mammal.

11. The method of claim 6, wherein said mammal is a human, canine, feline, rodent, sheep, goat, cattle, horse, pig, or non-human primate.

12. The method of claim 6, wherein said neural stem cells are obtained from the subventricular zone in the forebrain of said mammal and said oligodendrocyte precursor cells are obtained from the central nervous system of said mammal.

13. The method of claim 12, wherein said neural stem cells and/or oligodendrocyte precursor cells are obtained from a mammal selected from the group consisting of an embryonic mammal, a neonatal mammal, and an adult mammal.

14. The method of claim 6, further comprising applying an effective amount of triiodothyronine.

15. The method of claim 12, wherein the oligodendrocyte precursor cells are obtained from one or more of the optic nerve, corpus callosum, or spinal cord.

16. A method for treating or ameliorating a disease or condition associated with demyelination in a mammal comprising:

(a) culturing mammalian neural stem cell and/or oligodendrocyte precursor cells;

(b) transplanting said neural stem cell and/or oligodendrocyte precursor cells into a mammal; and

(c) administering a prolactin to said mammal in order to induce said neural stem cells and/or oligodendrocyte precursor cells to generate oligodendrocytes.

17. The method of claim 16, wherein said mammalian neural stem cell and/or oligodendrocyte precursor cell culture is prepared using mammalian brain tissue selected from the group consisting of embryonic brain tissue, neonatal brain tissue, and adult brain tissue.

18. The method of claim 16, wherein said neural stem cells are obtained from the subventricular zone in the forebrain of said mammal and said oligodendrocyte precursor cells are obtained from the central nervous system of said mammal.

19. The method of claim 18, wherein the oligodendrocyte precursor cells are obtained from one or more of the optic nerve, corpus callosum, or spinal cord.

20. The method of claim 16, further comprising applying an effective amount of triiodothyronine.

21. The method of claim 16, wherein said prolactin is administered intrathecally, intravascularly, intravenously, intramuscularly, intraperitoneally, transdermally, intradermally, subcutaneously, orally, topically, rectally, vaginally, nasally, or by inhalation.

22. The method of claim 16, wherein said prolactin is administered by injection or infusion.

23. The method of claim 16, wherein said mammalian neural stem cell and/or oligodendrocyte precursor cells are harvested from said mammal for autologous transplantation.

24. The method of claim 16, further comprising expanding said neural stem cell and/or oligodendrocyte precursor cells in vivo, by administering to said mammal a biological agent selected from the group consisting of epidermal growth factor (EGF), pituitary adenylate cyclase-activating polypeptide (PACAP), fibroblast growth factor (FGF), transforming growth factor alpha (TGFα

), ciliary neurotrophic factor (CNTF), Leukemia Inhibitory Factor (LIF), platelet-derived growth factor (PDGF), estrogen, ovarian hormone, human chorionic gonadotrophin (hCG), and insulin-like growth factor-1.

25. The method of claim 16, wherein said neural stem cells and/or oligodendrocyte precursor cells are introduced into the brain, optic nerve or spinal cord of said mammal.

26. The method of claim 25, wherein said neural stem cell and/or oligodendrocyte precursor cells are introduced into a site where axons have been demyelinated.

27. The method of claim 16, wherein said disease or condition associated with demyelination is selected from the group consisting of multiple sclerosis, acute disseminated encephalomyelitis, diffuse cerebral sclerosis, necrotizing hemorrhagic encephalitis, leukodystrophies, stroke, spinal cord injury, schizophrenia, bipolar disorder, acute brain injury, and dementia.

28. The method of claim 27, wherein said disease or condition is multiple sclerosis.

29. A method of delivering oligodendrocytes to a mammal, comprising administering to said mammal an effective amount of a pharmaceutical composition comprising:

(a) at least one neural stem cell and/or oligodendrocyte precursor cell; and

(b) an effective amount of a prolactin or prolactin releasing peptide to said mammal.

30. The method of claim 29, further comprising contacting said neural stem cells and/or oligodendrocyte precursor cells with at least one biological agent selected from the group consisting of epidermal growth factor (EGF), pituitary adenylate cyclase-activating polypeptide (PACAP), fibroblast growth factor (FGF), transforming growth factor alpha (TGFα

), ciliary neurotrophic factor (CNTF), Leukemia Inhibitory Factor (LIF), platelet-derived growth factor (PDGF), estrogen, ovarian hormone, human chorionic gonadotrophin (hCG), and insulin-like growth factor-1.

31. The method of claim 30, wherein said biological agent is used before said introduction of said neural stem cell and/or oligodendrocyte precursor cell into said mammal.

32. The method of claim 30, wherein said biological agent is used after said introduction of said neural stem cell and/or oligodendrocyte precursor cell into said mammal.

33. The method of claim 30, wherein said biological agent is used both before and after said introduction of said neural stem cell and/or oligodendrocyte precursor cell into said mammal.

34. The method of claim 29, wherein said mammal is a human, canine, feline, rodent, sheep, goat, cattle, horse, pig, or non-human primate.

35. The method of claim 29, wherein said neural stem cells are obtained from the subventricular zone in the forebrain of said mammal and said oligodendrocyte precursor cells are obtained from the central nervous system of said mammal.

36. The method of claim 35, wherein the oligodendrocyte precursor cells are obtained from one or more of the optic nerve, corpus callosum, or spinal cord.

37. The method of claim 35, wherein said neural stem cells and/or oligodendrocyte precursor cells are obtained from a mammal selected from the group consisting of an embryonic mammal, a neonatal mammal, and an adult mammal.

38. The method of claim 29, further comprising applying an effective amount of triiodothyronine.