METHODS FOR TREATING SEPTIC SHOCK

• US 20110053830A1
• Filed: 09/01/2010
• Published: 03/03/2011
• Est. Priority Date: 08/07/2006
• Status: Abandoned Application

• Current Assignee: Government of the United States of America, Oregon Health & Science University
• Original Assignee: Government of the United States of America, Oregon Health & Science University
• Inventors: McCoy, Sharon L., Hefeneider, Steve
• Application Number:
  US12/874,106
• Publication Number:
  US 20110053830A1
• Time in Patent Office: Days
• US Class Current: 514/1.4
• 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 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/162 from virus
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• 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
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods for the treatment of septic shock are disclosed herein. The methods include the use of a therapeutically effective amount of inhibitory peptides that inhibit TLR activity. The peptides can be used with other agents for the treatment of septic shock. In one embodiment, a therapeutically effective amount of a peptide is administered to a subject with septic shock, such as septic shock induced by an infection with gram negative bacteria.

Claims

1. A method for treating a subject with septic shock, comprising

selecting a subject with septic shock;

and

administering to the subject a therapeutically effective amount of a therapeutic polypeptide, wherein the therapeutic polypeptide consists of;

(a) a first polypeptide consisting of 11 to 18 consecutive amino acids of the amino acid sequence set forth in SEQ ID NO;

1 (A52R), or wherein the first polypeptide consists of 11 to 18 consecutive amino acids of amino acid sequence set forth as SEQ ID NO;

1 with a single amino acid substitution thereof, wherein the first retains the ability to inhibit Toll-like receptor activity as the 11 to 18 consecutive amino acids of the amino acid sequence set forth in SEQ ID NO;

1, and

(b) a second polypeptide consisting of seven to ten consecutive arginine residues,

thereby treating the septic shock in the subject.

2. The method of claim 1, wherein the first polypeptide consists of ten to twelve consecutive amino acids of the amino acid sequence set forth in SEQ ID NO:

1.

3. The method of claim 1, wherein the first polypeptide consists of twelve amino acids of the sequence set forth in SEQ ID NO:

1.

4. The method of claim 1, wherein second polypeptide consists of nine arginine residues.

5. The method of claim 1, wherein the first polypeptide consists of the amino acid sequence set forth as amino acids 70-86 of SEQ ID NO:

1.

6. The method of claim 1, wherein the first polypeptide consists of the amino acid sequence set forth as amino acids 70 to 86 of SEQ ID NO:

1 with a single amino acid substitution, wherein the first polypeptide retains the ability to inhibit Toll-like receptor activity as a polypeptide comprising amino acids 70-86 of SEQ ID NO;

1.

7. The method of claim 1, wherein the therapeutic polypeptide consists of amino acids 125-135 of SEQ ID NO:

1 or a single amino acid substitution thereof that retains the ability to inhibit Toll-like receptor activity.

8. The method of claim 1, wherein the subject is infected with a gram negative bacteria.

9. The method of claim 8, wherein the gram negative bacteria is Escherichia coli, Klebsiella pneumoniae, Proteus species, Pseudomonas aeruginosa or Salmonella typhimurium.

10. The method of claim 1, wherein the subject is infected with a gram positive bacteria.

11. The method of claim 10, wherein the gram positive bacteria is a species of Staphlococci, Streptococci or Pneumococci.

12. The method of claim 1, wherein the subject is infected with a fungus.

13. The method of claim 1, further comprising administering to the subject a therapeutically effective amount of an anti-microbial agent.

14. The method of claim 1, further comprising administering to the subject a therapeutically effective amount of a corticosteroid.

15. The method of claim 1, wherein the first polypeptide consists of the amino acid sequence set forth as SEQ ID NO:

3, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20 or SEQ ID NO;

21.

16. The method of claim 15, wherein the subject is infected with a gram negative bacteria.

17. The method of claim 1, wherein the therapeutic polypeptide is administered orally.