Methods and compositions for treatment of retinoid-responsive conditions

Abstract

Methods and composition for treating a retinoid-responsive condition in a subject are provided according to embodiments of the present invention which include administering a therapeutically effective amount of a substance selected from the group consisting of: neutrophil gelatinase-associated lipocalin (NGAL), an NGAL analog, an NGAL stimulator and an analog of an NGAL stimulator, to a subject having a retinoid-responsive condition. Retinoid-responsive conditions illustratively include acne, rosacea, psoriasis, promyelocytic leukemia and neuroblastoma.

1 . A method of treating retinoid-responsive condition in a subject, comprising:
 administering a therapeutically effective amount of a protein selected from: a protein comprising the amino acid of SEQ ID No. 1; a protein comprising the amino acid of SEQ ID No. 2; a protein encoded by the complement of a nucleic acid that hybridizes under highly stringent conditions with the nucleotide sequence of SEQ ID No. 3; a protein encoded by the complement of a nucleic acid that hybridizes under highly stringent conditions with the nucleotide sequence of SEQ ID No. 4; wherein the highly stringent conditions are: hybridization in a solution containing 6×SSC, 5×Denhardt's solution, 30% formamide, and 100 micrograms/ml denatured salmon sperm at 37° C. overnight followed by washing in a solution of 0.1×SSC and 0.1% SDS at 60° C. for 15 minutes; a protein comprising an amino acid sequence that is at least 95% identical to SEQ ID No. 1; and a protein comprising an amino acid sequence that is at least 95% identical to SEQ ID No. 2, to a subject having a retinoid-responsive condition.   
     
     
         2 . The method of  claim 1 , wherein the retinoid-responsive condition is selected from the group consisting of: acne, rosacea, psoriasis, promyelocytic leukemia and neuroblastoma 
     
     
         3 . The method of  claim 1 , wherein the protein is administered to skin affected by a retinoid-responsive condition selected from the group consisting of: acne, rosacea and psoriasis. 
     
     
         4 . The method of  claim 1 , wherein the protein is administered to skin affected by acne in the subject. 
     
     
         5 . A method of treating a retinoid-responsive condition in a subject, comprising:
 administering a therapeutically effective amount of a substance selected from the group consisting of: neutrophil gelatinase-associated lipocalin (NGAL), an NGAL analog, an NGAL stimulator and an analog of an NGAL stimulator, to a subject having a retinoid-responsive condition.   
     
     
         6 . The method of  claim 5 , wherein the NGAL analog is an NGAL receptor agonist. 
     
     
         7 . The method of  claim 5 , wherein the NGAL is encoded by a nucleic acid in an expression vector. 
     
     
         8 . The method of  claim 5 , wherein the NGAL stimulator is selected from the group consisting of: a Toll-like receptor 2 ligand, a Toll-like receptor 3 ligand, an activator of NFκB, leukotriene B4, cholesterol oleate and IL-17. 
     
     
         9 . The method of  claim 5 , wherein the activator of NFκB is selected from the group consisting of: IL1-beta and TNF-alpha. 
     
     
         10 . The method of  claim 8 , wherein the Toll-like receptor 2 ligand is N-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine. 
     
     
         11 . The method of  claim 8 , wherein the Toll-like receptor 3 ligand is polyinosinic:polycytidylic acid. 
     
     
         12 . The method of  claim 5 , wherein the retinoid-responsive condition is selected from the group consisting of: acne, rosacea, psoriasis, promyelocytic leukemia and neuroblastoma. 
     
     
         13 . The method of  claim 5 , wherein the substance is administered to skin affected by a retinoid-responsive condition selected from the group consisting of: acne, rosacea and psoriasis. 
     
     
         14 . The method of  claim 5 , wherein the substance is administered to skin affected by acne in the subject. 
     
     
         15 . A method of treating a retinoid-responsive condition in a subject, comprising:
 stimulating NGAL expression in a subject having acne.   
     
     
         16 . The method of treating a retinoid-responsive condition in a subject of  claim 15 , wherein NGAL expression is stimulated by administration of an NGAL stimulator which upregulates transcription of a gene encoding NGAL. 
     
     
         17 . The method of treating acne in a subject of  claim 15 , wherein NGAL expression is stimulated by administration of a nucleic acid encoding NGAL to the subject. 
     
     
         18 . The method of  claim 16 , wherein the NGAL stimulator is selected from the group consisting of: a Toll-like receptor 2 ligand, a Toll-like receptor 3 ligand, an activator of NFκB, leukotriene B4, cholesterol oleate and IL-17. 
     
     
         19 . The method of  claim 18 , wherein the activator of NFκB is selected from the group consisting of: IL1-beta and TNF-alpha. 
     
     
         20 . The method of  claim 18 , wherein the Toll-like receptor 2 ligand is N-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine. 
     
     
         21 . The method of  claim 18 , wherein the Toll-like receptor 3 ligand is polyinosinic:polycytidylic acid. 
     
     
         22 . A method of inhibiting  Propionibacterium acnes , comprising:
 contacting a  Propionibacterium acnes  bacterium with a substance selected from the group consisting of: NGAL and an NGAL analog.   
     
     
         23 . The method of inhibiting  Propionibacterium acnes  of  claim 22 , wherein the  Propionibacterium acnes  bacterium is in contact with a human subject. 
     
     
         24 . The method of inhibiting  Propionibacterium acnes  of  claim 23 , wherein the human subject has acne. 
     
     
         25 . The method of inhibiting  Propionibacterium acnes  of  claim 23 , wherein the human subject has rosacea. 
     
     
         26 . A composition for treating a retinoid-responsive condition in a subject, comprising a substance selected from the group consisting of: neutrophil gelatinase-associated lipocalin (NGAL), an NGAL analog, an NGAL stimulator, an analog of an NGAL stimulator and a combination of two or more of: neutrophil gelatinase-associated lipocalin (NGAL), an NGAL analog, an NGAL stimulator and an analog of an NGAL stimulator. 
     
     
         27 . The composition of  claim 26 , wherein the NGAL stimulator is selected from the group consisting of: a Toll-like receptor 2 ligand, a Toll-like receptor 3 ligand, an activator of NFκB, N-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine, polyinosinic:polycytidylic acid, leukotriene B4, cholesterol oleate, IL-17 and a combination of two or more of a Toll-like receptor 2 ligand, a Toll-like receptor 3 ligand, an activator of NFκB, N-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine, polyinosinic:polycytidylic acid, leukotriene B4, cholesterol oleate and IL-17. 
     
     
         28 . The composition of  claim 26 , wherein the substance is selected from: a protein comprising the amino acid of SEQ ID No. 1; a protein comprising the amino acid of SEQ ID No. 2; a protein encoded by the complement of a nucleic acid that hybridizes under highly stringent conditions with the nucleotide sequence of SEQ ID No. 3; a protein encoded by the complement of a nucleic acid that hybridizes under highly stringent conditions with the nucleotide sequence of SEQ ID No. 4; wherein the highly stringent conditions are: hybridization in a solution containing 6×SSC, 5×Denhardt's solution, 30% formamide, and 100 micrograms/ml denatured salmon sperm at 37° C. overnight followed by washing in a solution of 0.1×SSC and 0.1% SDS at 60° C. for 15 minutes; a protein comprising an amino acid sequence that is at least 95% identical to SEQ ID No. 1; and a protein comprising an amino acid sequence that is at least 95% identical to SEQ ID No. 2, to a subject having a retinoid-responsive condition.