Methods and compositions for control of fetal growth via modulation of relaxin

Abstract

The invention relates to the method for treatment, diagnosis and prevention of diseases related to fetal growth and placental insufficiency and comprises methods including inhibiting or increasing relaxin synthesis, relaxin receptor synthesis, relaxin binding to the relaxin receptor, and relaxin receptor activity. The invention also relates to screening assays to identify compounds that modulate relaxin and/or relaxin receptor activity. The invention further relates to gene therapy methods utilizing relaxin and relaxin-related sequences for the treatment and prevention of diseases related to fetal growth and placental insufficiency.

1 . A method of reducing the risk or incidence of spontaneous abortion in a pregnant mammal, the method comprising administering to the pregnant mammal an amount of relaxin effective to reduce the risk or incidence of spontaneous abortion.  
   
   
       2 . The method of  claim 1 , wherein the relaxin is administered during the first trimester of pregnancy.  
   
   
       3 . The method of  claim 1 , wherein the relaxin is administered during the second trimester of pregnancy.  
   
   
       4 . The method of  claim 1 , wherein the relaxin is administered for at least 2 weeks, starting at ovulation.  
   
   
       5 . The method of  claim 1 , wherein the relaxin is before and after ovulation.  
   
   
       6 . The method of  claim 1 , wherein the relaxin is administered for about one week before and about 4 weeks after ovulation.  
   
   
       7 . The method of  claim 1 , wherein the relaxin is administered in an amount sufficient to maintain serum concentration of at least about 1 ng/ml.  
   
   
       8 . A method for determining whether a subject has an increased risk for developing a condition associated with placental insufficiency, the method comprising: 
 measuring the level of relaxin expression in said subject; and    comparing said measured level of relaxin to a level of relaxin associated with normal placental development in an appropriate control subject;    wherein a lower measured level of relaxin correlates with an increased risk of developing a condition associated with placental insufficiency.    
   
   
       9 . The method of  claim 8 , wherein said condition associated with placental insufficiency is selected from the group consisting of IUGR, SGR and preeclampsia.  
   
   
       10 . The method of  claim 8 , wherein said level of relaxin expression is measured in serum.  
   
   
       11 . The method of  claim 8 , wherein said level of relaxin expression is measured in tissue.  
   
   
       12 . The method of  claim 8 , wherein said level of relaxin expression is measured by determining the level of transcription of a gene encoding relaxin.  
   
   
       13 . The method of  claim 8 , wherein said level of relaxin expression is measured by determining the level of an enzyme involved in post-translational processing of relaxin.  
   
   
       14 . The method of  claim 13 , wherein said level of an enzyme involved in post-translational processing of relaxin is measured by determining the level of transcription of gene encoding said enzyme.  
   
   
       15 . The method of  claim 1 , wherein said relaxin is selected from the group consisting of H1, H2 or H3 relaxin.  
   
   
       16 . The method of  claim 15 , wherein said relaxin is H2 relaxin.  
   
   
       17 . The method of  claim 8 , wherein said relaxin is selected from the group consisting of H1, H2 or H3 relaxin.  
   
   
       18 . The method of  claim 17 , wherein said relaxin is H2 relaxin.  
   
   
       19 . The method of  claim 8 , wherein the subject is pregnant.  
   
   
       20 . The method of  claim 8 , wherein the subject has been diagnosed with IUGR, placental insufficiency or preeclampsia.  
   
   
       21 . The method of  claim 8 , further comprising the step of treating said subject with a therapeutic amount of relaxin.