XENOTRANSPLANT FOR CNS THERAPY

• US 20090181064A1
• Filed: 03/05/2009
• Published: 07/16/2009
• Est. Priority Date: 04/30/1999
• Status: Abandoned Application

• Current Assignee: Neurotrophincell Pty, Limited
• Original Assignee: Neurotrophincell Pty, Limited
• Inventors: Williams, Christopher Edward, Elliott, Robert Bartlett, Skinner, Stephen John Martin
• Application Number:
  US12/398,642
• Publication Number:
  US 20090181064A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• 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 35/30 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: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3878 Nerve tissue, brain, spinal cord, nerves, dura mater
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: C12N 5/0618 Cells of the nervous system
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

Abstract

A “supplementary choroid plexus” comprising preferably a xenotransplant of choroid plexus cells from a neonatal mammal provides a steady supply of trophic factors for administration to a central nervous system in need of treatment for a neurological disease. Choroid plexus cells manufacture a range of trophic factors, particularly during fetal development. This neurotrophic factor therapy may be useful in treating clinical and subclinical neurodegenerative diseases particularly those in which the choroid plexus has often become atrophic. The xenotransplant is cloaked in a protective layer (such as of alginate) capable of concealing the foreign nature of the transplant. Lateral ventricles are the preferred implantation site, from where the trophic factors are carried through the neuropil by the circulation of cerebrospinal fluid.

Claims

1. An implant, for implantation into the brain of a recipient mammal, having Huntington'"'"'s chorea, said implant comprising a population of living non-human choroid epithelial cells that are encapsulated within a biocompatible capsule, the wall of said capsule at least partially composed of a semi-permeable membrane, wherein said membrane admits metabolites for sustaining said cells and permits a therapeutically-effective amount of one or more factors selected from the group consisting of IGF, TGF-a, RA, NGF, VEG and FGF to exit from said implant into said brain.

15. The implant of claim 1, wherein said non-human choroid epithelial cells express at least one neurotransmitter.

16. The implant of claim 15, wherein said neurotransmitter comprises dopamine.

17. The implant of claim 1, wherein said non-human choroid epithelial cells express at least one product that modulates the response of at least some cells of the central nervous system of said recipient mammal to at least one neurotransmitter.

18. The implant of claim 17, wherein the modulation of said response is mediated by enhancing the binding of said neurotransmitter to its receptor.

19. The implant of claim 18, wherein said neurotransmitter comprises dopamine.

20. The implant of claim 1, wherein said non-human choroid epithelial cells express at least one factor that supports the growth of at least some cells of the central nervous system.

21. The implant of claim 1, wherein said biocompatible capsule comprises at least one inner layer that comprises laminin;

said laminin serving as a substrate for said non-human choroid epithelial cells.

22. The implant of claim 1, wherein said biocompatible capsule further comprises at least one globular containment means for holding a portion of said non-human choroid epithelial cells.

23. The implant of claim 1, wherein said biocompatible capsule further comprises at least one tubular containment means for holding a portion of said non-human choroid epithelial cells.

24. The implant of claim 1, wherein said recipient mammal is human.

25. The implant of claim 1, wherein said non-human choroid epithelial cells are obtained from the choroids plexus of a fetal or neonatal non-human mammal.

26. The implant of claim 1, wherein said non-human choroid epithelial cells are porcine.

27. The implant of claim 1, wherein said membrane further blocks access to said implant by factors of the immune system of said recipient mammal.

28. The implant of claim 17, wherein said biocompatible capsule comprises alginate.

31. A kit comprising, in suitable container means, the implant of claim 1 or claim 29, and a liquid medium that maintains said implant in a living condition for a period of time.

2-14. -14. (canceled)

29. An implant, for implantation into the brain of a recipient human having Huntington'"'"'s chorea, said implant comprising a population of living porcine choroid epithelial cells encapsulated within a biocompatible capsule that comprises alginate, wherein the wall of said biocompatible capsule comprises a semi-permeable membrane that admits metabolites for sustaining said cells, blocks access to said implant by factors of the immune system of said recipient human, and permits a therapeutically-effective amount of one or more factors selected from the group consisting of IGF, TGF-α

, RA, NGF, VEG and FGF to exit from said implant into said brain for a time sufficient to treat Huntington'"'"'s chorea.

30. An implant, for implantation into the brain of a recipient human having Huntington'"'"'s chorea, said implant comprising a population of living porcine choroid epithelial cells that are encapsulated within a biocompatible capsule, comprising alginate, wherein the wall of said capsule at least partially comprises a semi-permeable membrane that admits metabolites for sustaining said cells, blocks access to said implant by factors of the immune system of said recipient human, and permits a therapeutically-effective amount of one or more factors selected from the group consisting of IGF, TGF-α

, RA, NGF, VEG and FGF to exit from said implant into said ventricle for a time sufficient to treat said Huntington'"'"'s chorea.