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Analysis by Tufts Medical Center and Tufts University researchers suggests that oxidative stress is strongly evident in the in-utero environment of Down syndrome fetus
Abnormal gene expression in amniotic fluid could play role in suggesting potential therapies for Down syndrome
Journal article
BOSTON (May 27, 2009) – A paper published today in the Proceedings of the National Academy of Sciences by researchers at Tufts Medical Center and Tufts University reports that amniotic fluid surrounding Down syndrome fetuses shows oxidative stress, a condition that could harm fetal cells and potentially play a role in affected individuals. The results suggest there are secondary adverse consequences of Down syndrome that are evident by the second trimester of pregnancy, leading to pathways to explore potential novel prenatal therapies for diagnosed fetuses.
Diana Bianchi, M.D., Vice Chair for research in the 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’s School of Engineering, conducted an analysis of the human genome from cell-free fetal messenger RNA floating in the amniotic fluid that surrounds fetuses with Down syndrome and normal fetuses. The researchers identified significant molecular changes that were evident in the Down syndrome fetuses as early as the fourth month of pregnancy.
Down syndrome occurs when an individual has three copies of chromosome 21 instead of the usual two copies. The longstanding assumption about Down syndrome has been that extra proteins produced by the additional copy of chromosome 21 were almost exclusively responsible for the abnormal 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, in addition to more modest changes in expression of the genes on chromosome 21.
As a next step, the 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 in laboratory tests.
“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 that this abnormal environment is not conducive to optimal development.”
The research relied heavily on computational analysis and bioinformatics. The data were analyzed by several competing methods. Slonim notes, “One exciting feature of this work is that, while different analytical methods implicated different and independent sets of genes, they all pointed to the same underlying processes: oxidative stress and its consequences.”
To support their conclusions, the researchers applied the Connectivity Map, a tool that links information about genomics and FDA-approved compounds to suggest possible drug therapies for various disease pathways. This approach further implicated the same underlying processes, and suggests important directions for future work.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Award to Bianchi and a Tufts Mellon Research Fellowship to Slonim.
About Tufts Medical Center
Tufts Medical Center is an exceptional, not-for-profit, 451-bed academic medical center that is home to both a full-service hospital for adults and Floating Hospital for Children. Conveniently located in downtown Boston, the Medical Center is the principal teaching hospital for Tufts University School of Medicine. Floating Hospital for Children is the full-service children's hospital of Tufts Medical Center and the principal pediatric teaching hospital of Tufts University School of Medicine. For more information, please visit www.tuftsmedicalcenter.org.
About Tufts University
Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.
Media Contact:
Julie Jette
(617) 636-3265
jjette@tuftsmedicalcenter.org
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