Methods for treating back or neck pain caused by NGF using a therapeutic agent consisting of ReN-1820, ALE-0540 and capsaicin

Patent metadata

Field	Value
Publication number	US-9789161-B2
Application number	US-41468906-A
Country	US
Kind code	B2
Filing date	Apr 28, 2006
Priority date	Apr 28, 2006
Publication date	Oct 17, 2017
Grant date	Oct 17, 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 wherein the pain is caused by NGF, the method consisting of:
providing a therapeutic agent consisting of an effective amount of ReN-1820, ALE-0540 and capsaicin encapsulated in a depot comprising microbubbles comprising a protective coating for timed local release and having a polymer comprising polyaspirins or poly(N-isopropylacrylamide) that provides for timed local release; and
subjecting the microbubbles to sonic energy to release the effective amount of ReN-1820, ALE-0540 and capsaicin to at least an annulus fibrosus region or a nucleus pulposus region of a disc, said ReN-1820 being a soluble receptor to NGF and provided to disrupt a neuronal element in at least the annulus fibrosus region or the nucleus pulposus region of the disc and a vascular element in at least the annulus fibrosus region or the nucleus pulposus region of the disc,
wherein the depot comprises a pore forming agent comprising polyethylene glycol (PEG) and an excipient in an amount of from 50% to 99.9% by weight based on a total weight of the depot.

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

3. The method of claim 1 , wherein ReN-1820 destroys, forces retraction or blocks further growth of the neuronal element or vascular element in at least the annulus fibrosus region of the disc.

4. The method of claim 3 , wherein ReN-1820 reduces nerve growth factor (NGF), or the response of the neuronal element or vascular element to the NGF.

5. The method of claim 1 , wherein the excipient comprises 98% by weight based on the total amount of the depot.

6. The method of claim 1 , wherein the excipient comprises 99.9% by weight based on the total amount of the depot.

7. The method of claim 1 , wherein the ALE-0540 reduces pain and inflammation caused by NGF in the at least annulus fibrosus region or the nucleus pulposus region of the disc.

8. The method of claim 1 , wherein the disc is a degenerated disc; and the excipient is in the depot in an amount of 99.9% by weight based on the total amount of the depot.

9. A method for treating back or neck pain with or without radiculopathy wherein the pain is caused by NGF, the method consisting of:
providing a therapeutic agent consisting of an effective amount of ReN-1820, ALE-0540 and capsaicin encapsulated in a depot comprising microbubbles comprising a protective coating for timed local release and having a polymer comprising polyaspirins or poly(N-isopropylacrylamide) that provides for timed local release; and
subjecting the microbubbles to sonic energy to release the effective amount of ReN-1820, ALE-0540 and capsaicin to at least a nucleus pulposus region of a disc, said ReN-1820 provided to disrupt a neuronal element in at least the nucleus pulposus of the disc and a vascular element in at least the nucleus pulposus of the disc,
wherein the depot comprises a pore forming agent comprising polyethylene glycol (PEG) and an excipient in an amount of from 98% to 99.9% by weight based on a total weight of the depot.

10. The method of claim 9 , wherein the disc is a degenerated disc.

11. The method of claim 9 , wherein the ReN-1820 destroys, forces retraction or blocks further growth of the neuronal element or vascular element in at least the nucleus pulposus of the disc.

12. The method of claim 9 , wherein the ReN-1820 reduces nerve growth factor (NGF), or the response of the neuronal element or vascular element to the NGF.

13. The method of claim 9 wherein said back and neck pain is caused by spinal compression.

14. A method for treating back or neck pain with or without radiculopathy wherein the pain is caused by NGF, the method consisting of:
providing an effective amount of at least one active ingredient configured to disrupt a neuronal element in at least the annulus fibrosus region or the nucleus pulposus region of the disc and a vascular element in at least the annulus fibrosus region or the nucleus pulposus region of the disc, the active ingredient consisting of ReN-1820, ALE-0540 and capsaicin encapsulated in microbubbles comprising a protective coating for timed local release;
conjugating the at least one active ingredient to a monoclonal antibody to keratan sulfate configured to selectively target a degenerated disc; and
delivering the at least one active ingredient conjugated to the antibody systemically to a patient having back or neck pain via sonic energy such that the microbubbles release the active ingredient.

Assignees

• Roy Josee
• Drapeau Susan J
• Marx Jeffrey C
• Warsaw Orthopedic Inc

Inventors

• Roy Josee
• Drapeau Susan J
• Marx Jeffrey C

Classifications

• A61K38/185

  Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3 · CPC title

• C07K2317/51

  Complete heavy chain or Fd fragment, i.e. VH + CH1 · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title