Ceramide levels in the treatment and prevention of infections

Patent metadata

Field	Value
Publication number	US-10159724-B2
Application number	US-201615286327-A
Country	US
Kind code	B2
Filing date	Oct 5, 2016
Priority date	Jun 1, 2012
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The present invention relates to a method for treating or preventing pathogenic infections in a subject having Cystic Fibrosis, COPD, and/or an open wound. This method involves selecting a subject having Cystic Fibrosis, COPD, and/or an open wound and administering to the selected subject a ceramidase under conditions effective to reduce ceramide and to treat or prevent the pathogenic infection. The method also involves the use of a ceramidase in combination with other drugs to reduce infection, reduce ceramide, or improve lung function in Cystic Fibrosis, COPD, and/or open wound patients.

First claim

What is claimed:

1. A method for treating pathogenic infections in a subject having Cystic Fibrosis, COPD, and/or an open wound, said method comprising:
selecting a subject having Cystic Fibrosis, COPD, and/or an open wound and
administering to said selected subject a ceramidase under conditions effective to reduce ceramide in said selected subject.

2. The method of claim 1 , wherein the subject is selected based on elevated ceramide levels compared to a reference level for a subject not having said Cystic Fibrosis, COPD, and/or an open wound.

3. The method of claim 1 , wherein said selecting is based on ceramide level in lung epithelium, nasal epithelium, mucus, and/or cells isolated from an open wound site.

4. The method of claim 1 , wherein said administering is carried out under conditions effective to normalize ceramide levels in the subjects' respiratory epithelia, mucus, or cells at an open wound site.

5. The method of claim 1 , wherein said ceramidase is acid ceramidase.

6. The method of claim 1 , wherein one or more additional agents that reduce ceramide levels are administered in combination with said ceramidase.

7. The method of claim 6 , wherein said one or more additional agents are selected from the group consisting of one or more additional ceramide reducing agents, one or more acid sphingomyelinase inhibitors, one or more agents to reduce infection, and combinations thereof.

8. The method of claim 7 , wherein said one or more additional agents is one or more agents to reduce infection and is selected from the group consisting of antibiotics, reagents that block binding of pathogens to lung epithelium, reagents to reduce mucus viscosity, chaperone reagents to enhance missing protein function, and combinations thereof.

9. The method of claim 7 , wherein said ceramidase is administered simultaneously, separately, or sequentially with said one or more additional agents.

10. The method of claim 1 , wherein said administering is oral, topical, intranasal, intraperitoneal, intravenous, subcutaneous, or by aerosol inhalation.

11. The method of claim 10 , wherein said administering is by aerosol inhalation.

12. The method of claim 1 , wherein the ceramidase is administered in an amount from 0.001 mg/kg to 500 mg/kg.

13. The method of claim 1 , wherein said selected subject is suffering from a viral, fungal, prionic, or bacterial infection.

14. The method of claim 13 , wherein said selected subject is suffering from a bacterial infection.

15. The method of claim 14 , wherein said selected subject is suffering from a Pseudomonas infection.

16. The method of claim 15 , wherein said Pseudomonas infection is a Pseudomonas aeruginosa infection.

17. The method of claim 1 , wherein said ceramidase is administered after onset of infection.

18. The method of claim 1 , wherein the selected subject has Cystic Fibrosis.

19. The method of claim 1 , wherein the selected subject has COPD.

20. The method of claim 1 , wherein the selected subject has an open wound.

Assignees

• Icahn School Med Mount Sinai
• Yeda Res And Development Co Ltd At The Weizmann Institute Of Science
• Univ Duisburg Essen

Inventors

• Schuchman Edward H
• Gulbins Erich
• Futerman Anthony
• Pewzner-Jung Yael

Classifications

• A61P31/06

  for tuberculosis · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C12Y305/01023

  Ceramidase (3.5.1.23) · CPC title