Hmgb1 antagonist treatment of diabetic peripheral neuropathy

Patent metadata

Field	Value
Publication number	US-2020353037-A1
Application number	US-202016869950-A
Country	US
Kind code	A1
Filing date	May 8, 2020
Priority date	May 9, 2019
Publication date	Nov 12, 2020
Grant date	—

Abstract

The present invention is related to the use of HMGB1 antagonists, specifically derivatives of K883 in the treatment and/or prevention and/or inhibition of neuropathy pain, and in particular diabetic neuropathy in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists in an effective amount to treat and/or prevent and/or inhibit this condition.

First claim

What is claimed is:

1 . A method of treating and/or inhibiting neuropathic pain in a mammal comprising administering to a mammal a therapeutically effective amount of a peptidomimetic small molecule modeled after an HMGB1 antagonist tetramer peptide.

2 . The method of claim 1 , wherein the peptidomimetic small molecule is an HMGB1 antagonist tetramer peptide which has been stabilized with at least one azatide linkage.

3 . The method of claim 2 , wherein the peptidomimetic small molecule is a modified P5779 wherein at least one terminal peptide bond has been replaced with an azatide linkage.

4 . The method of claim 2 , wherein the peptidomimetic small molecule peptidomimetic small molecule is a modified P5779 wherein the terminal peptide bonds have been replaced with azatide linkages.

5 . The method of claim 2 , wherein the peptidomimetic small molecule is K883.

6 . The method of claim 1 , wherein the mammal is a human.

7 . The method of claim 1 , wherein the method of administration is selected from the group consisting of oral delivery, parenteral delivery, buccal delivery, sublingual delivery, nasal delivery, inhalation delivery, nebulization delivery, topical delivery, transdermal delivery and suppository delivery.

8 . A method of treatment of neuropathic pain, comprising identifying a human patient exhibiting symptoms of DPN, and administering K883.

9 . A method of preparing a treatment for neuropathic pain, comprising modifying P5779 with at least one azatide linkage.

10 . The method of claim 8 , wherein the modified P5779 has at least one azatide linkage located at a terminal peptide bond.

11 . The method of claim 10 , wherein the modified P5779 is K883.

12 . The method of claim 5 , wherein the K883 is combined with an excipient comprising PBS:PEG 300:propylene glycol:polysorbate 80 at 50:40:5:5.

13 . The method of claim 7 , wherein the therapeutically effective amount is orally administered to the mammal.

14 . The method of claim 7 , wherein the therapeutically effective amount is intravenously administered to the mammal.

15 . The method of claim 7 , wherein the mammal is human.

16 . The method of claim 1 wherein the neuropathic pain is diabetic neuropathic pain.

17 . The method of claim 1 , wherein the peptidomimetic small molecule is a derivative of K883 or P5779.

18 . The method of claim 3 , wherein the aqueous solubility of the modified P5779 is greater than about 1 mg/ml.

19 . The method of claim 3 , wherein the modified P5779 is stable for greater than 60 minutes in plasma or simulated stomach acid.

20 . The method of claim 9 , wherein the modified P5779 is K883.

Assignees

• Feinstein Institutes For Medical Research

Inventors

• Al-Abed Yousef
• Yang Huan

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C07K5/1016

  and aromatic or cycloaliphatic · CPC title

• C07K5/06069

  Ser-amino acid · CPC title

• C07K1/113

  without change of the primary structure · CPC title

• A61P25/02 Primary

  for peripheral neuropathies · CPC title