Jan. 20, 2009 To better understand preeclampsia, a sudden rise in maternal blood pressure and onset of kidney disease during pregnancy, researchers from Cornell University and Weill Cornell Medical College are studying mice that have the same affliction. Preeclampsia is the leading cause of both maternal and fetal death — killing more than 500,000 women worldwide each year and causing 15 percent of all premature births — yet the condition is not well understood.
Dr. Robin Davisson, Dr. Shari Gelber, and their team of researchers have developed an experimental gene therapy technique that lessens preeclampsia in mice, with the hope of someday applying their promising findings to humans. Dr. Davisson is a professor of cell and developmental biology at Weill Cornell Medical College and professor of molecular physiology at Cornell University's College of Veterinary Medicine, in Ithaca, New York. Dr. Shari Gelber is a clinical fellow in maternal-fetal medicine in the department of obstetrics and gynecology at Weill Cornell Medical College in New York City.
To test their therapy, Dr. Davisson and Dr. Gelber have identified a type of mouse, called the BPH/5 mouse, that demonstrates features similar to those seen in humans with preeclampsia.
They have observed that these mice have a blood pressure spike late in the second trimester or early in the third trimester of pregnancy, as well as high protein found in the urine because of impaired kidney function — all of which mimic the clinical signs of preeclampsia in humans. They also have smaller litters of pups, both in number and in birth weight.
Currently, it is a mystery as to who is at a greater risk for preeclampsia, because the disease does not show symptoms until late in gestation. What experts do know is that there is a shallow invasion, or weak connection, between the placenta and the mother's uterus — which is also seen in the BPH/5 mice. The research team is studying the BPH/5 mice with the hope of understanding the disease in early gestation, and to test a gene therapy technique that boosts a growth factor and improves blood circulation between the mother and fetus.
To administer the gene therapy, Dr. Davisson and her colleagues have injected mice with a harmless virus that contains a gene that, when taken up by the body, raises secretions of VEGF endothelial growth factor. The molecule helps blood vessel growth in the placenta, creating a better connection between the mother and fetus. The research team was encouraged to find that the experimental mice did not have a blood pressure spike or high levels of protein in the urine, compared with normal mice that received a virus injection that lacked the VEGF-producing gene. The experimental mice also have more normal litter sizes and the mouse pups weigh more.
During pregnancy, a preeclamptic mother suffers from elevated blood pressure, which can develop into eclampsia, causing stroke, liver failure, internal bleeding, postpartum hemorrhage, seizure, coma and death. The only known way to treat the condition is to deliver the fetus, usually before term. There is a risk of fetal death and low birth weight, which raises the risk of childhood seizures, blindness and pediatric asthma.
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The above story is based on materials provided by New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College.
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