Compositions and methods for the treatment of myelin related and inflammation related diseases or disorders

Abstract

Described are oxysterols, pharmaceutical compositions including the oxysterols, and methods of using the oxysterols and compositions for treating diseases and/or disorders related to inflammation, such as necrotizing enterocolitis, mesenteric ischemia, inflammatory bowel diseases including Crohn's disease and ulcerative colitis, lymphocytic colitis, Celiac disease, Behcet's disease, rheumatoid arthritis, psoriasis, and autoimmune thyroid disease.

1 .- 25 . (canceled) 
     
     
         26 . A method of slowing and/or preventing disease or disorder progression in a subject in need thereof, the method comprising:
 administering to a subject at risk of developing or diagnosed with a disease or disorder characterized by inflammation a therapeutically effective amount of one or more oxysterols, wherein, following the administering step, the disease or disease-related inflammation is reduced.   
     
     
         27 . The method of  claim 26 , wherein the one or more oxysterols comprise 20α-hydroxycholesterol, 22(R)-hydroxycholesterol, 22(S)-hydroxycholesterol, 24(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, a pharmaceutically acceptable salt thereof, or any combination thereof. 
     
     
         28 . The method of  claim 26 , wherein the disease or disorder characterized by inflammation comprises rheumatoid arthritis, psoriasis, or autoimmune thyroid disease. 
     
     
         29 . The method of  claim 26 , wherein the disease or disorder characterized by inflammation comprises necrotizing enterocolitis, mesenteric ischemia, Crohn's disease, ulcerative colitis, lymphocytic colitis, Celiac disease, or Behcet's disease. 
     
     
         30 . The method of  claim 29 , wherein the subject is a premature infant at risk of developing necrotizing enterocolitis. 
     
     
         31 . The method of  claim 26 , further comprising measuring the level of NF-κB activation in a sample obtained from the subject. 
     
     
         32 . The method of  claim 31 , wherein following the administering of the one or more oxysterols, the level of NF-κB activation is about that of a control sample. 
     
     
         33 . The method of  claim 32 , wherein when the level of NF-κB activation is about that of a control sample, inflammation in the subject is reduced. 
     
     
         34 . The method of  claim 26 , further comprising measuring the level of TH17 polarization in sample obtained from the subject. 
     
     
         35 . The method of  claim 34 , wherein following the administering of the one or more oxysterols, the level of TH17 polarization is about that of a control sample. 
     
     
         36 . The method of  claim 35 , wherein when the level of TH17 polarization is about that of a control sample, inflammation in the subject is reduced. 
     
     
         37 . The method of  claim 26 , further comprising administering to the subject an additional therapeutic agent, wherein the additional therapeutic agent is administered in combination, simultaneously, or sequentially with the one or more oxysterols. 
     
     
         38 . The method of  claim 37 , wherein the additional therapeutic agent comprises an antibiotic or an immunosuppressant. 
     
     
         39 . The method of  claim 38 , wherein the antibiotic comprises ampicillin, gentamycin, zosyn, vancomycin, or a combination thereof. 
     
     
         40 . The method of  claim 38 , wherein the immunosuppressant comprises a corticosteroid or a non-steroidal anti-inflammatory agent. 
     
     
         41 . The method of  claim 26 , wherein the one or more oxysterols exist in a pharmaceutical formulation. 
     
     
         42 . The method of  claim 26 , wherein administering the one or more oxysterols comprises oral, intravenous, or transdermal administration. 
     
     
         43 . A method of treating a subject in need thereof, the method comprising:
 slowing and/or preventing an inflammation-related disease or disorder by administering to a subject at risk of developing or diagnosed with a disease or disorder characterized by inflammation a therapeutically effective amount of one or more oxysterols, wherein, following the administering step, the level of NF-κB activation and/or the level of TH17 polarization are reduced.   
     
     
         44 . The method of  claim 43 , wherein the one or more oxysterols comprise 20α-hydroxycholesterol, 22(R)-hydroxycholesterol, 22(S)-hydroxycholesterol, 24(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, a pharmaceutically acceptable salt thereof, or any combination thereof. 
     
     
         45 . The method of  claim 43 , wherein the disease or disorder characterized by inflammation comprises necrotizing enterocolitis, mesenteric ischemia, Crohn's disease, ulcerative colitis, lymphocytic colitis, Celiac disease, or Behcet's disease.