Ameliorating nervous systems disorders

Patent metadata

Field	Value
Publication number	US-9220729-B2
Application number	US-201313744201-A
Country	US
Kind code	B2
Filing date	Jan 17, 2013
Priority date	May 6, 2008
Publication date	Dec 29, 2015
Grant date	Dec 29, 2015

Abstract

The present disclosure provides methods for the treatment of a mammal having a neurological condition, disease, or injury. The methods involve increasing the number of functional GABAergic interneurons at or near the site of the neurological disease, injury, or condition.

First claim

What is claimed is:

1. A method for the treatment of a mammal having Parkinson's disease comprising:
depositing MGE (medial ganglionic eminence) precursor cells at desired delivery sites in the brain to increase the number of functional DARPP32 negative GABAergic interneurons in the brain,
wherein said DARPP32 negative GABAergic interneurons functionally integrate with endogenous neurons; and
assessing the functional integration of the DARPP32 negative GABAergic interneurons resulting from the deposition of the MGE precursor cells by assessing an improvement of the symptoms of the Parkinson's disease in the treated mammal.

2. The method of claim 1 , wherein the MGE precursor cells are deposited by injection.

3. The method of claim 2 , wherein the MGE precursor cells are injected into the striatum, basal ganglia, dorsal ganglia, ventral horn, or lumbar theca.

4. The method as in claim 2 , wherein the mammal does not require immunosuppressive therapy following treatment.

5. The method of claim 2 , wherein the MGE precursor cells are injected in or near the striatum.

6. The method of claim 1 , wherein the MGE precursor cells are deposited into the striatum.

7. The method of claim 2 , wherein the MGE precursor cells are able to migrate at least 0.5 mm from the transplantation site.

8. The method of claim 7 , wherein the deposited MGE precursor cells result in at least a 10% reduction in required antispasmodic drug use.

9. The method of claim 1 , wherein the wherein deposition of MGE precursor cells results in at least a 10% reduction in required anti-Parkinsonian drug use.

10. The method of claim 1 , wherein deposition of MGE precursor cells results in at least a 10% reduction in tremor at rest, rigidity, akinesia, bradykinesia, postural instability, flexed posture and/or freezing.

11. The method of claim 1 , wherein the MGE cells are deposited into the striatum, and wherein the deposited MGE cells survive for at least 6 months.

12. A method for the treatment of a mammal with spasticity, comprising:
depositing MGE precursor cells at desired delivery sites to increase the number of functional DARPP32 negative GABAergic interneurons,
wherein said DARPP32 negative GABAergic interneurons functionally integrate with endogenous neurons; and
assessing the functional integration of the DARPP32 negative GABAergic interneurons resulting from the deposition of the MGE precursor cells by assessing an improvement of the spasticity in the treated mammal.

13. The method of claim 12 , wherein the deposited MGE precursor cells obviates the need for intrathecal medication or surgery.

14. The method of claim 12 , wherein the MGE precursor cells are deposited by injection.

15. The method of claim 14 , wherein the MGE precursor cells are injected into the brain, spinal cord or peripheral nervous system.

16. The method of claim 14 , wherein the MGE precursor cells are able to migrate at least 0.5 mm from the site of injection.

17. The method of claim 12 , wherein the deposition of MGE precursor cells results in a reduction of spasticity resulting from nerve injury.

18. The method of claim 12 , wherein the nerve injury is a spinal cord injury.

19. The method as in claim 12 , wherein the mammal does not require immunosuppressive therapy following treatment.

20. A method for the treatment of a mammal with a chronic pain disorder, comprising:
depositing MGE precursor cells at desired delivery sites in the mammal to increase the number of functional DARPP32 negative GABAergic interneurons,
wherein said DARPP32 negative GABAergic interneurons functionally integrate with endogenous neurons; and
assessing the functional integration of the DARPP32 negative GABAergic interneurons resulting from the deposition of the MGE precursor cells by assessing an improvement of the symptoms of the chronic pain disorder in the treated mammal.

21. The method of claim 20 , wherein the deposition of MGE precursor cells results in a reduction of pain resulting from nerve injury.

22. The method of claim 21 , wherein the nerve injury is a spinal cord injury.

23. The method of claim 22 , wherein deposition of MGE precursor cells results in a reduction of neuropathic pain resulting from a spinal cord injury.

24. The method of claim 20 , wherein the MGE precursor cells are deposited by injection.

25. The method of claim 24 , wherein the MGE precursor cells are injected into the brain, spinal cord or peripheral nervous system.

26. The method as in claim 20 , wherein the mammal does not require immunosuppressive therapy following treatment.

27. A method for the treatment of a mammal with a spinal cord injury, comprising:
depositing MGE precursor cells in or near the spinal cord to increase the number of functional DARPP32 negative GABAergic interneurons,
wherein said DARPP32 negative GABAergic interneurons functionally integrate with endogenous neurons in or near the spinal cord; and
assessing the functional integration of the DARPP32 negative GABAergic interneurons resulting from the deposition of the MGE precursor cells by assessing an improvement of the spinal cord injury in the treated mammal.

28. The method of claim 27 , wherein the MGE precursor cells are deposited by injection.

29. The method of claim 28 , wherein the MGE precursor cells are able to migrate at least 0.5 mm from the site of injection.

30. The method as in claim 27 , wherein the mammal does not require immunosuppressive therapy following treatment.

Assignees

• Univ California

Inventors

• Kriegstein Arnold
• Rubenstein John L R
• Baraban Scott C
• Alvarez-Buylla Arturo

Classifications

• G01N2800/2835

  Movement disorders, e.g. Parkinson, Huntington, Tourette · CPC title

• A61K35/30 Primary

  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 title

• C12N5/0622

  Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• C12N5/0618

  Cells of the nervous system · CPC title