Prevention of preterm birth (ptb) by inhibition of fkbp51

Abstract

The disclosure is directed to a method of enhancing progesterone receptor (PR) activity in a mammal, which comprises administering a composition comprising an inhibitor of FK506 binding protein 51 (FKBP51) to a mammal in need thereof, such as a pregnant human female, whereby progesterone receptor activity in the mammal is enhanced as compared to a mammal not administered the composition. The method results in an extension of the gestation period and a decreased likelihood of preterm birth and fetal growth restriction.

1 . A method of preventing or treating fetal growth restriction in a pregnant mammal comprising administering a composition comprising an inhibitor of FK506 binding protein 51 (FKBP51) to the pregnant mammal, whereby fetal growth restriction is prevented or treated as compared to a pregnant mammal that is not administered the composition, and wherein the inhibitor of FKBP51 is 15-deoxy-Δ12,14-prostaglandin J2 or a small interfering RNA (siRNA). 
     
     
         2 . The method of  claim 1 , wherein the inhibitor of FKBP51 enhances progesterone receptor (PR) activity in the pregnant mammal as compared to a pregnant mammal not administered the composition. 
     
     
         3 . The method of  claim 2 , wherein the PR activity is PR-mediated gene transcription. 
     
     
         4 . The method of  claim 1 , wherein the inhibitor of FKBP51 blocks glucocorticoid-induced FKBP51 gene expression. 
     
     
         5 . The method of  claim 4 , wherein the glucocorticoid is dexamethasone (DEX). 
     
     
         6 . The method of  claim 1 , wherein the gestation period of the pregnant mammal is extended as compared to a pregnant mammal that is not administered the composition. 
     
     
         7 . The method of  claim 1 , wherein the likelihood of preterm birth (PTB) is reduced as compared to a pregnant mammal not administered the composition. 
     
     
         8 . The method of  claim 1 , wherein the pregnant mammal is under stress. 
     
     
         9 . The method of  claim 1 , wherein the pregnant mammal has an increased level of IL-8 as compared to a reference control prior to the administration. 
     
     
         10 . The method of  claim 1 , wherein the pregnant mammal does not have an increased level of IL-6 as compared to a reference control prior to the administration. 
     
     
         11 . The method of  claim 1 , wherein the pregnant mammal does not have an increased level of TNF-α as compared to a reference control prior to the administration.