Use of TGF-Beta Antagonists to Treat Infants at Risk of Developing Bronchopulmonary Dysplasia

Abstract

The disclosure relates to methods of treating an infant at risk of developing bronchopulmonary dysplasia, including premature infants, by administering a TGF-β antagonist during the perinatal period, including the prenatal period and/or the postnatal period. For administration during the prenatal period, the TGF-β antagonist can be administered either directly to the infant in utero, or indirectly by administration to the mother.

1 - 25 . (canceled) 
     
     
         26 . A method of increasing lung alveologenesis and/or vasculogenesis in an infant or fetus, comprising: administering a therapeutically effective amount of a TGFβ antagonist to the infant or fetus. 
     
     
         27 . The method of  claim 26 , wherein the method increases peripheral lung alveologenesis and/or vasculogenesis in the infant or fetus. 
     
     
         28 . The method of  claim 26 , wherein the method decreases mean cord length of the infant or fetus lung by at least 10%. 
     
     
         29 . The method of  claim 26 , wherein the method decreases alveolar volume density of the infant or fetus lung by at least 20%. 
     
     
         30 . The method of  claim 26 , wherein the method increases secondary septal density of the infant or fetus lung by at least 20%. 
     
     
         31 . The method of  claim 26 , wherein the method decreases elastin volume density of the infant or fetus lung by at least 20%. 
     
     
         32 . The method of  claim 26 , wherein the method increases elastin and/or αSMA expression in the infant or fetus peripheral lung. 
     
     
         33 . The method of  claim 26 , wherein the TGF-β antagonist is administered during the perinatal, prenatal, or postnatal period. 
     
     
         34 . The method of  claim 26 , wherein the TGF-β antagonist is administered directly to the infant or fetus in utero or indirectly to said infant or fetus by administration to the mother prior to birth of the infant. 
     
     
         35 . The method of  claim 26 , wherein the TGF-β antagonist is administered intramuscularly, intravenously or subcutaneously. 
     
     
         36 . The method of  claim 26 , wherein the TGF-β antagonist is administered directly to the lung in an aerosolized form. 
     
     
         37 . The method of  claim 26 , wherein the infant is of an age of about 24 weeks gestation to about 6 months after birth. 
     
     
         38 . The method of  claim 26 , wherein the weight of the infant at birth is about 1500 grams or less. 
     
     
         39 . The method of  claim 26 , wherein the TGF-β antagonist is selected from the group consisting of an anti-TGF-β antibody, an anti-TGFβ receptor antibody, and a soluble TGFβ receptor. 
     
     
         40 . The method of  claim 26 , wherein the TGF-β antagonist is a pan-specific human antibody or a humanized monoclonal antibody. 
     
     
         41 . The method of  claim 26 , wherein the TGF-β antagonist is a human or humanized form of monoclonal anti-TGF-β antibody 1D11. 
     
     
         42 . The method of  claim 26 , wherein the TGFβ antagonist is administered with an additional agent or therapy selected from surfactant, oxygen therapy, ventilator therapy, a steroid, vitamin A, inhaled nitric oxide, high calorie nutritional formulation, a diuretic and a bronchodilator. 
     
     
         43 . A method of treating inhibition of alveologenesis and/or vasculogenesis in an injured lung of an infant or fetus, comprising: administering a therapeutically effective amount of a TGF-β antagonist to the infant or fetus. 
     
     
         44 . The method of  claim 43 , wherein the method:
 i) increases peripheral lung alveologenesis and/or vasculogenesis in the infant or fetus;   ii) decreases mean cord length of the infant or fetus lung by at least 10%;   iii) decreases alveolar volume density of the infant or fetus lung by at least 20%;   iv) increases secondary septal density of the infant or fetus lung by at least 20%;   v) decreases elastin volume density of the infant or fetus lung by at least 20%; and/or   vi) increases elastin and/or αSMA expression in the infant or fetus peripheral lung.   
     
     
         45 . The method of  claim 43 , wherein the TGF-β antagonist is administered to infant or fetus and the method further comprises administering oxygen supplementation to the infant after birth.