Ceramide levels in the treatment and prevention of infections

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.

1 .- 20 . (canceled) 
     
     
         21 . A method for treating a pathogenic infection in a subject, said method comprising:
 selecting a subject having a pathogenic infection and   administering to said selected subject a recombinant acid ceramidase under conditions effective to reduce ceramide and to treat said pathogenic infection in said selected subject.   
     
     
         22 . The method of  claim 21 , wherein said pathogenic infection comprises a bacterial pathogen, a viral pathogen, or a fungal pathogen. 
     
     
         23 . The method of  claim 21 , wherein the subject has a disease condition which predisposes the subject to pathogenic infections. 
     
     
         24 . The method of  claim 23 , wherein the disease condition is selected from the group consisting of respiratory disease, lung disease, emphysema, asthma, pulmonary fibrosis, chronic bronchitis, pneumonia, pulmonary hypertension, lung cancer, sarcoidosis, necrotizing pneumonia, asbestosis, aspergilloma, aspergillosis, acute invasive atelectasis, eosinophilic pneumonia, pleural effusion, pneumoconiosis, pneumocystosis, pneumothorax, pulmonary actinomycosis, pulmonary alveolar proteinosis, pulmonary anthracis, pulmonary arteriovenous malformation, pulmonary edema, pulmonary embolus, pulmonary histiocytosis X (eosinophilic granuloma), pulmonary nocardiosis, pulmonary tuberculosis, pulmonary veno-occlusive disease, and rheumatoid lung disease. 
     
     
         25 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises an acid ceramidase precursor protein. 
     
     
         26 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises an acid ceramidase precursor protein and an active acid ceramidase. 
     
     
         27 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises UniProt Q13510, UniProt Q9H715, UniProt Q96AS2, OMIM 228000, NCBI Gene 427, NCBI RefSeq NP_808592, NCBI RefSeq NP_004306, NCBI RefSeq NM_177924, NCBI RefSeq NM_004315, NCBI UniGene 427, NCBI Accession Q13510, NCBI Accession AAC73009, or a combination thereof. 
     
     
         28 . The method of  claim 21 , wherein said selecting is based on ceramide level in lung epithelium, nasal epithelium, mucus, or isolated cells. 
     
     
         29 . The method of  claim 21 , wherein said administering is carried out under conditions effective to normalize ceramide levels in the subjects' respiratory epithelia, mucus, or cells. 
     
     
         30 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises an active acid ceramidase protein. 
     
     
         31 . The method of  claim 21 , wherein one or more additional agents that reduce ceramide levels are administered in combination with said recombinant acid ceramidase. 
     
     
         32 . The method of  claim 31 , 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. 
     
     
         33 . The method of  claim 31 , 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. 
     
     
         34 . The method of  claim 21 , wherein said recombinant acid ceramidase is administered simultaneously, separately, or sequentially with said one or more additional agents. 
     
     
         35 . The method of  claim 21 , wherein said administering is oral, intranasal, intraperitoneal, intravenous, subcutaneous, or by aerosol inhalation. 
     
     
         36 . The method of  claim 21 , wherein said administering is by topical administration. 
     
     
         37 . The method of  claim 21 , wherein said administering is by aerosol inhalation. 
     
     
         38 . The method of  claim 21 , wherein the ceramidase is administered in an amount from 0.001 mg/kg to 500 mg/kg. 
     
     
         39 . The method of  claim 21 , wherein said recombinant acid ceramidase is administered prior to onset of infection. 
     
     
         40 . The method of  claim 21 , wherein said recombinant acid ceramidase is administered after onset of infection. 
     
     
         41 . The method of  claim 21 , wherein the subject has Cystic Fibrosis. 
     
     
         42 . The method of  claim 21 , wherein the subject has COPD. 
     
     
         43 . The method of  claim 21 , wherein the subject has an open wound.