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Researchers Suggest That Oxidative Stress is Strongly Evident in the In-Utero Environment of the Fetus With Down Syndrome
Date:6/2/2009

Abnormal gene expression in amniotic fluid could play role in suggesting potential therapies

BOSTON, June 2 /PRNewswire-USNewswire/ -- A paper published in the Proceedings of the National Academy of Sciences (http://www.pnas.org/content/early/2009/05/27/0903909106) by Tufts Medical Center and Tufts University researchers reports that amniotic fluid surrounding Down syndrome fetuses shows oxidative stress, a condition that could harm fetal cells and play a role in affected individuals. The results demonstrate secondary adverse consequences of Down syndrome and suggest potential prenatal therapies.

Diana Bianchi, M.D., Vice Chair for Research, Department of Pediatrics at Floating Hospital for Children at Tufts Medical Center, and Donna Slonim, Ph.D., Associate Professor of Computer Science at Tufts University, conducted an analysis of the human genome from cell-free fetal messenger RNA in amniotic fluid surrounding fetuses. Their team identified molecular and biochemical pathway changes that were evident in the Down syndrome fetuses as compared to normal fetuses as early as the fourth month of pregnancy.

Down syndrome occurs when an individual has three copies of chromosome 21 instead of two. The longstanding assumption has been that proteins produced by the additional copy of chromosome 21 were almost exclusively responsible for the atypical development and function associated with the syndrome. A surprising aspect of the findings was that the molecular abnormalities observed were predominantly produced by genes on the other chromosomes.

As a next step, researchers are examining amniotic cells to determine if they show similar genomic profiles to the cell-free material in the fluid. If that is the case, they will begin to look at the effectiveness of anti-oxidant compounds as potential treatment in vitro.

"While more research is needed, this study illuminates a possible pathway to treating some aspects of Down syndrome in the womb," Bianchi said. "While we do not know the extent to which the developing fetus is affected by oxidative stress, we know this abnormal environment is not conducive to optimal development."

The analysis relied heavily on computer analysis and bioinformatics. To support their conclusions, the researchers applied the Connectivity Map, a tool linking information about genomics and FDA-approved compounds to suggest drug therapies for various disease pathways. This approach implicated the same underlying processes, and suggests directions for future work.


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SOURCE Tufts Medical Center
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