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Biological Chemistry

Hope For Preeclampsia Victims

Finding may aid diagnosis, treatment of pregnancy condition

by Rachel Petkewichh
May 19, 2008 | A version of this story appeared in Volume 86, Issue 20

Better diagnosis and treatment of preeclampsia could emerge from a new finding that a deficiency in a steroid hormone metabolite may trigger the dangerous pregnancy condition (Nature, DOI: 10.1038/nature06951).

Preeclampsia is a hypertensive condition that occurs in at least 5% of pregnant women worldwide, with potentially life-threatening consequences for mother and baby. The condition usually appears after 20 weeks of pregnancy and is currently diagnosed by symptoms such as high blood pressure and excessive protein in urine.

Delivering the baby is the best treatment for a mother with preeclampsia. But if the baby is fewer than 32 weeks old, doctors may treat the mother's symptoms with drugs until the baby matures.

However, drugs for preeclampsia may have adverse consequences for the mother and fetus. "A natural compound with low toxicity would be a substantial improvement," says Jerome F. Strauss, a coauthor of the paper and dean of medicine at Virginia Commonwealth University.

To find such a compound, Strauss, Raghu Kalluri at Harvard Medical School, and colleagues genetically engineered mice to have preeclampsia-like symptoms by knocking out a gene that makes the enzyme catechol-O-methyltransferase (COMT). The researchers observed that the modification also caused the mice to lack 2-methoxyestradiol (2ME), a natural estrogen metabolite produced by COMT that usually increases during the last trimester of human pregnancy.

They noted that women with preeclampsia also have low levels of COMT and 2ME, suggesting that a problem with the COMT gene is responsible for the condition. The discovery may lead to a simple test for 2ME in urine to diagnose preeclampsia and to a 2ME supplement that might prevent the condition, according to the researchers.

The results may explain how preeclampsia occurs and could point toward future therapies, but more work is needed before they can be translated to patient care, says Asif Ahmed, a professor of reproductive and vascular biology at the University of Birmingham, England. He is also principal investigator of a large study of pregnant women in the U.K. that will further explore the roles of COMT and 2ME in preeclampsia.

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