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Gene Therapy Studied for Preeclampsia

New Clues to a Mysterious Pregnancy Condition

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.

Busted Spine-Discs? Grow New Ones!

Researchers Are Bioengineering Intervertebral Discs (IVD)

Each year, 40 to 60 percent of American adults suffer from chronic back pain. For patients diagnosed with severe degenerative disc disease, neurosurgeons must perform surgery called discectomy — removing the IVD — followed by a fusion of the vertebrate bones to stabilize the spine. Even after all that effort, the patient's back will likely not feel the same as before their injury. But collaboration between physician-scientists at Weill Cornell Medical College and basic science researchers at Cornell University has led to the creation of bioengineered IVDs, in the laboratory, for transplantation into the spines of rats.

To create new spine discs, Dr. Roger Härtl and Dr. Lawrence Bonassar are using cells from IVD tissue of human patients who have had their spinal discs removed. Dr. Härtl is a noted neurological surgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and the Leonard and Fleur Harlan Clinical Scholar and assistant professor of neurological surgery at Weill Cornell Medical College, and Dr. Bonassar is an associate professor in the departments of biomedical engineering and mechanical and aerospace engineering at Cornell University in Ithaca, New York.

Dr. Härtl harvests tissue from the removed discs and sends it to Dr. Bonassar. Cells are then isolated from this tissue and grown in an incubator that simulates the environment in the body. Once developed, they are placed on a bioengineered scaffold, enabling the assembly of the cells and scaffold into an IVD-shaped implant. The research team then surgically implants the discs inside a rat's spine in order to see how the tissue reacts to the mechanical and biological demands. So far, results are promising. The researchers hope to soon test the bioengineered discs in human subjects in a clinical trial, so that someday people can receive spare parts for their aging or injured backs.

The Genetic Fingerprint of Prostate Cancer

How Estrogen Might Play a Role

One in six American men are diagnosed with prostate cancer within their lifetime and 186,000 will be diagnosed this year. For most men, their disease is confined to the prostate gland, making it easier to treat and less lethal. However, some unfortunate patients suffer from a more aggressive cancer that metastasizes, or spreads beyond the boundaries of the prostate gland. Physician-scientists are trying to uncover part of the disease's molecular fingerprint, with the hope of explaining why some forms metastasize. Their findings may help physicians provide tailored, and therefore, more effective treatments for patients.

Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College, and attending pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, believes that the common joining of two genes to form a new fusion gene influences a certain type of prostate cancer that is more aggressive and sensitive to hormones. In a recent article published in the Journal of the National Cancer Institute, Dr. Rubin describes how in addition to the male hormone testosterone, estrogen — typically thought of as a female hormone — can stimulate this fusion gene. Dr. Rubin's group is currently exploring how this mechanism may help us understand how aggressive prostate cancer progresses in the absence of male hormones.

Currently, Dr. Rubin and his colleague Dr. Francesca Demichelis, assistant professor in pathology and laboratory medicine and computational biomedicine at the Institute of Computational Biomedicine at Weill Cornell Medical College, are testing blood samples and comparing the DNA of over 2,500 men with and without prostate cancer. They hope to discover clear genetic indicators of prostate cancer, especially its aggressive forms. Their findings will potentially lead to the development of diagnostic tests and preventive drugs for prostate cancer.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and www.med.cornell.edu.