Methods and compositions for control of fetal growth via modulation of relaxin
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 increasing intrauterine fetal growth rate, the method comprising administering to a primate in need thereof a therapeutically effective amount of relaxin sufficient to maintain a serum concentration of at least about 1-2 ng/mL in said primate in order to increase fetal growth rate, wherein said relaxin is administered parenterally or by continuous subcutaneous infusion during the second trimester of pregnancy.
2. The method of claim 1 , wherein the relaxin is further administered during the first trimester of pregnancy.
3. The method of claim 1 , wherein the relaxin is further administered during the third trimester of pregnancy.
4. The method of claim 1 , wherein the relaxin is administered in an amount sufficient to result in the birth of a baby of at least around normal birth weight.
5. The method of claim 1 , wherein the relaxin is administered in an amount sufficient to maintain a serum concentration of at least around 1 ng/mL.
6. The method of claim 1 , wherein the relaxin is administered parenterally.
7. The method of claim 1 , wherein the relaxin is administered by continuous subcutaneous infusion.
8. The method of claim 7 , wherein the relaxin is administered at a dose between 10 μg/kg/day and 200 μg/kg/day.
9. The method of claim 1 , wherein the increase in fetal growth rate is assessed by an imaging technique.
10. The method of claim 9 , wherein the imaging technique is chosen from the group consisting of ultrasonic imaging and magnetic resonance imaging.
11. The method of claim 1 , wherein the primate is diagnosed as hosting a fetus with intrauterine growth retardation.
12. The method of claim 11 , wherein the diagnosis is by an imaging technique.
13. The method of claim 12 , wherein the imaging technique is chosen from the group consisting of ultrasonic imaging and magnetic resonance imaging.
14. The method of claim 1 , wherein the primate has a condition that increases the risk of fetal intrauterine growth retardation.
15. The method of claim 14 , wherein the condition is selected from the group consisting of lupus, hyperthyroidism, hypertension, preeclampsia, malarial infection, serum antiphospholipid antibodies, a history of recent spontaneous abortion, a history of intrauterine growth retardation, a history of having children with low birth weight, a multiple gestation pregnancy, and a pregnancy resulting from in vitro fertilization and embryo transfer.
16. The method of claim 1 , wherein the primate is a human.
17. The method of claim 1 , wherein the primate is a nonhuman primate.