Ceramide levels in the treatment and prevention of infections

Patent metadata

Field	Value
Publication number	US-9492514-B2
Application number	US-201314404881-A
Country	US
Kind code	B2
Filing date	May 31, 2013
Priority date	Jun 1, 2012
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

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 improving pathogenic clearance 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 therapeutically effective amount of ceramidase under conditions effective to reduce ceramide and improve pathogenic clearance of a Pseudomonas pathogen 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 Pseudomonas pathogen is Pseudomonas aeruginosa.

14. The method of claim 1 , wherein said ceramidase is administered prior to onset of infection.

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

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

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

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

Assignees

• Icahn School Med Mount Sinai
• Yeda Res And Dev Co Ltd At The Weizmann Inst Of Science
• Univ Duisburg-Essen
• Univ Duisberg-Essen

Inventors

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

Classifications

• A61P31/06

  for tuberculosis · CPC title

• A61P31/00

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

• A61P31/04

  Antibacterial agents · CPC title

• A61K9/0073

  Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M) · CPC title

• A61K38/50 Primary

  acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase · CPC title