Pharmaceutical removal of neuronal extensions from a degenerating disc

Patent metadata

Field	Value
Publication number	US-9730986-B2
Application number	US-201414577307-A
Country	US
Kind code	B2
Filing date	Dec 19, 2014
Priority date	Apr 28, 2006
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

The invention provides a method for alleviating discogenic pain by administering a therapeutic agent that disrupts neuronal and/or vascular elements in the disc, which is typically a degenerated disc. Disruption of neuronal elements in the disk includes destroying nerve endings without substantially affecting the central body of the nerve, suppressing activation of the nerve endings, and inhibiting the growth of nerve endings into the disk. Disruption of vascular elements includes causing the vascular extensions to retract from the disk, or suppressing the formation of such extensions. The therapeutic agent may be administered locally via an interbody pump, a bolus or a depot, or may be administered systemically.

First claim

What is claimed is:

1. A method for treating back or neck pain with or without radiculopathy comprising locally delivering a depot, wherein the depot comprises a bolus of microbubbles and provides an effective amount of a therapeutic agent to a disc region comprising a disc, the therapeutic agent adapted to disrupt a neuronal element in the disc region, wherein the therapeutic agent is selected from 8-Methyl-N-vanillyl-trans-6-nonenamide (Capsaicin), ReN-1820 for reducing the levels of NGF that can bind to NGF receptors found on neuronal elements, and a synthetic neurotoxin; and subjecting the depot to sonic energy to release the therapeutic agent from the depot within the disc region.

2. The method of claim 1 , wherein the disc is a degenerated disc.

3. The method of claim 1 , wherein the therapeutic agent is adapted to destroy, force retraction or block further growth of the neuronal element innervating the disc region.

4. The method of claim 3 , wherein the therapeutic agent modulates at least one growth factor, or modulates the response of the neuronal element to at least one growth factor.

5. The method of claim 4 , wherein the growth factor is selected from a set consisting of nerve growth factor, brain-derived growth factor, glial-derived growth factor, neurotrophin-3, neurotrophin-4, insulin-growth factor, fibroblast growth factor and leukemia inhibitory factor.

6. The method of claim 3 , wherein the therapeutic agent modulates at least one extra-cellular matrix component, or modulates the response of the neuronal element to the at least one extra-cellular matrix component.

7. The method of claim 6 , wherein the extra-cellular matrix component is selected from a set consisting of chondroitin sulfate proteglycans, netrins, semaphorins and myelin/oligodendrocyte growth inhibitors.

8. The method of claim 7 , wherein the myelin/oligodendrocyte growth inhibitors are selected from a set consisting of Nogo, MAG and OMgp.

9. The method of claim 6 , wherein the extra-cellular matrix component is a cell adhesion molecule.

10. The method of claim 9 , wherein the cell adhesion molecule is selected from a set consisting of NCAM, N-cadherins and integrins.

11. The method of claim 3 , wherein the therapeutic agent modulates a cytoskeletal component of the neuronal elements.

12. The method of claim 11 , wherein the cytoskeletal component is selected from a set consisting of actins, tubulins and neurofilaments.

13. The method of claim 1 , wherein the therapeutic agent is adapted to desensitize the neuronal element innervating the disc region.

14. The method of claim 1 , wherein the therapeutic agent is adapted to modulate a receptor or a molecule that binds to a receptor of the neuronal element innervating the disc region.

15. The method of claim 14 , wherein the therapeutic agent is adapted to modulate neuronal receptors selected from a set consisting of nociceptors, vanilloid, adrenergic, cholinergic, glutamate, GABA, serotonine, somatostatin opioids, ATP, Na+, K+, Ca2+, cannabinoids, Substance P and neuropeptide receptors.

16. The method of claim 1 , wherein the therapeutic agent is adapted to block the modulation of neuronal elements by a pro-inflammatory molecule.

17. The method of claim 16 , wherein the pro-inflammatory molecule is selected from a set consisting of cytokines, chemokines, neuropeptides, bradykinin, histamines and prostaglandins.

18. The method of claim 1 , wherein the therapeutic agent is adapted to modulate glial cells.

19. The method of claim 1 , wherein the depot comprises a biopolymer containing polylactide.

Assignees

• Warsaw Orthopedic Inc

Inventors

• Roy Josee
• Drapeau Susan J
• Marx Jeffrey C

Classifications

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/225

  Polycarboxylic acids · CPC title

• A61K38/4893 Primary

  Botulinum neurotoxin (3.4.24.69) · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• C12Y304/24069

  Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin · CPC title