METHODS FOR TREATING SPINAL CORD INJURY

• US 20190117724A1
• Filed: 06/22/2018
• Published: 04/25/2019
• Est. Priority Date: 10/21/2011
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Massachusetts Eye And Ear Infirmary (Foundation of The Massachusetts Eye and EAR Infirmary Incorporated)
• Original Assignee: Children's Medical Center Corporation, Massachusetts Eye And Ear Infirmary (Foundation of The Massachusetts Eye and EAR Infirmary Incorporated)
• Inventors: Vavvas, Demetrios G., Benowitz, Larry, Miller, Joan W.
• Granted Patent: US 10,799,552 B2
• Time in Patent Office: Days
• 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 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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 9/00 Drugs for disorders of the cardiovascular system

Abstract

Provided are methods for promoting axon regeneration of a Central Nervous System (CNS) neuron and promoting nerve function following injury to a CNS neuron, for example, brain and/or spinal cord injury. Axon regeneration in a CNS neuron or nerve function following injury to a CNS neuron can be promoted by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject suffering from a CNS disorder, wherein a symptom of the CNS disorder is axon degeneration.

Claims

1. A method for treating a Central Nervous System (CNS) disorder in a subject by promoting axon regeneration in a CNS neuron, the method comprising:

exposing the CNS neuron of the subject to an effective amount of a necrostatin and an effective amount of an apoptosis inhibitor thereby to promote the regeneration of the axon of the CNS neuron;

wherein the necrostatin is selected from the group consisting of;

(i) a Nec-1 related compound of Formula I;

2. The method of claim 1, wherein the neuron is ex vivo.

3. The method of claim 1, wherein the neuron is in vivo.

11. The method of claim 1, wherein the CNS neuron is selected from the group consisting of a sensory neuron, a motor neuron, a cortical neuron, a pyramidal neuron, a cerebellar neuron, a hippocampal neuron, and a midbrain neuron.

19. The method of claim 1, wherein the necrostatin is selected from the group consisting of necrostatin-1, necrostatin-2, necrostatin-3, necrostatin-4, necreostatin-5, and necrostatin-7, or a combination thereof.

20. The method of claim 1, wherein from about 0.05 mg to about 2 mg of the necrostatin is administered.

21. The method of claim 1, wherein the apoptosis inhibitor is a pan-caspase inhibitor.

22. The method of claim 21, wherein the pan-caspase inhibitor is zVAD, IDN-6556 or a combination thereof.

24. The method of claim 1, wherein the necrostatin, the apoptosis inhibitor, or both the necrostatin and the apoptosis inhibitor are administered locally.

25. The method of claim 1, wherein the necrostatin, the apoptosis inhibitor, or both the necrostatin and the apoptosis inhibitor are administered systemically.

26. The method of claim 1, wherein the necrostatin, the apoptosis inhibitor, or both the necrostatin and the apoptosis inhibitor are administered sequentially or simultaneously.

45. The method of claim 1, wherein the CNS disorder is ALS.

46. The method of claim 1, wherein the CNS disorder is Parkinson'"'"'s disease.

47. The method of claim 1, wherein the CNS disorder is multiple sclerosis.

48. The method of claim 1, wherein the CNS disorder is diabetic neuropathy.

49. The method of claim 1, wherein the CNS disorder is Friedreich'"'"'s ataxia.

50. The method of claim 1, wherein the CNS disorder is a CNS disorder arising from CNS neuron injury, and the CNS neuron injury is selected from the group consisting of surgery, nerve compression, nerve contusion, nerve transection, neurotoxicity, and physical injury to the brain.

51. The method of claim 1, wherein the CNS disorder is selected from the group consisting of injury to the brainstem and aneurysm in the brain stem.

52. The method of claim 1, wherein the CNS disorder is selected from the group consisting of frontotemporal dementia and dementia with Lewy bodies.

53. The method of claim 1, wherein the CNS disorder is selected from the group consisting of corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy, hereditary spastic paraparesis, and a spinocerebellar atrophy.

4-10. -10. (canceled)

12-18. -18. (canceled)

23. (canceled)

27-44. -44. (canceled)