Targeted epigenetic therapy for inherited aortic aneurysm condition

Abstract

Transforming growth factor β (TGFβ) transcriptional responses are involved in the pathogenesis of aortic aneurism syndromes. Compositions that inhibit histone acetyltransferase activity normalize gene expression in the aorta, preserved aortic wall architecture and abrogated aneurism progression. Methods include the use of these compositions to epigenetically regulate abnormal expression and/or activity of TGFβ genes.

1 - 20 . (canceled) 
     
     
         21 . A method for treating an aortic aneurysm syndrome, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of one or more inhibitors of TGFβ expression and/or activity, thereby treating the aortic aneurysm syndrome in the subject. 
     
     
         22 . The method of  claim 21 , wherein an aortic aneurysm syndrome comprises Shprintzen-Goldberg syndrome (SGS), Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), Ehlers-Danlos syndrome (EDS), familial aortic dissection, or annuloaortic ectasia. 
     
     
         23 . The method of  claim 21 , wherein the one or more TGFβ inhibitors modulate acetylation of histone H3K27 and/or normalize TGFβ synthetic repertoire (TSR) expression. 
     
     
         24 . The method of  claim 21 , wherein the TGFβ inhibitor is SD208 or Alk5. 
     
     
         25 . The method of  claim 21 , wherein the subject is a mammal. 
     
     
         26 . The method of  claim 25 , wherein the mammal is a human. 
     
     
         27 . The method of  claim 21 , wherein administering is via systemic administration