Targeting the Steroidogenic Pathway For Treating and/or Preventing Allergic Diseases

Abstract

The present invention relates to methods and compositions for treating and/or preventing allergic diseases or conditions by inhibiting one or more components of the steroidogenic pathway.

1 . A method of treating or preventing an allergic disease in a subject who has, or is at risk of developing an allergic disease, comprising administering to the subject a therapeutically effective amount of a steroidogenic pathway inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the allergic disease is selected from the group consisting of an allergic lung disease, allergen-induced airway hyperresponsiveness, allergen-induced inflammation, rhinitis, asthma, allergic rhinitis, food allergy, eosinophilic esophagitis, chronic urticaria, atopic dermatitis, occupational allergy, allergic conjunctivitis, hay fever, airborne allergic sensitivities, stinging insect allergy, hypersensitivity pneumonitis, eosinophilic lung diseases, inflammatory bowel disease, ulcerative colitis, and Crohn's disease. 
     
     
         3 . The method of  claim 2 , wherein the allergic disease is caused by one or more proteinaceous allergens. 
     
     
         4 . The method of  claim 1 , wherein the subject has been sensitized to an allergen or is at risk of becoming exposed to an allergen. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the steroidogenic pathway inhibitor is selected from the group consisting of an antibody, an antisense molecule, an siRNA molecule, an shRNA molecule, a receptor antagonist, a chemical entity, a nucleotide, a peptide, and a protein. 
     
     
         8 . The method of  claim 7 , wherein the steroidogenic pathway inhibitor inhibits one or more enzymes, receptors or protein by-products of the steroidogenic pathway. 
     
     
         9 . The method of  claim 8 , wherein the steroidogenic pathway inhibitor inhibits cytochrome P450 family 11 subfamily A polypeptide 1 (Cyp11A1). 
     
     
         10 . The method of  claim 9 , wherein the steroidogenic pathway inhibitor is selected from the group consisting of aminoglutethimide or a Cyp11A1 siRNA and a Cyp11A1 shRNA molecule. 
     
     
         11 . The method of  claim 8 , wherein the steroidogneic pathway inhibitor inhibits 3βHSD. 
     
     
         12 . The method of  claim 11 , wherein the steroidogenic pathway inhibitor is trilostane. 
     
     
         13 . The method of  claim 8 , wherein the steroidogneic pathway inhibitor inhibits cytochrome P450 family 11 subfamily β polypeptide 1 (Cyp11β1). 
     
     
         14 . The method of  claim 13 , wherein the steroidogenic pathway inhibitor is metyrapone. 
     
     
         15 . A method of inhibiting T-cell pro-allergic differentiation in a subject comprising administering to the subject a therapeutically effective amount of a steroidogenic pathway inhibitor. 
     
     
         16 . The method of  claim 15 , wherein the T-cell pro-allergic differentiation is CD4+ T-cells to Th2 and Th17 cell differentiation. 
     
     
         17 . The method of  claim 15 , wherein the T-cell pro-allergic differentiation is CD8+ T-cells to Tc2 cell differentiation. 
     
     
         18 . The method of  claim 15 , wherein the T-cell pro-allergic differentiation is IL4-induced conversion of CD8+ T-cells into IL-13 secreting cells. 
     
     
         19 . The method of  claim 15 , wherein the T-cell pro-allergic differentiation is IL-4 induced conversion of CD4+ T-cells into IL-13 secreting cells. 
     
     
         20 . The method of  claim 15 , wherein the subject has an allergic disease selected from the group consisting of a allergic lung disease, allergen-induced airway hyperresponsiveness, allergen-induced inflammation, rhinitis, asthma, allergic rhinitis, food allergy, eosinophilic esophagitis, chronic urticaria, atopic dermatitis, occupational allergy, allergic conjunctivitis, hay fever, airborne allergic sensitivities, stinging insect allergy, hypersensitivity pneumonitis, eosinophilic lung diseases, inflammatory bowel disease, ulcerative colitis, and Crohn's disease. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 15 , wherein the steroidogenic pathway inhibitor is selected from the group consisting of an antibody, an antisense molecule, an siRNA molecule, a chemical entity, a nucleotide, a peptide, and a protein. 
     
     
         25 . The method of  claim 24 , wherein the steroidogenic pathway inhibitor inhibits one or more enzymes or protein by-products of the steroidogenic pathway selected from the group consisting of Cyp11A1, 3βHSD, and Cyp11β1. 
     
     
         26 - 31 . (canceled)