Study Unravels Origin Of Down Syndrome

Stem cells have expanded research in many arenas -- the latest of which is in studying Down syndrome.

Using stem cells as a window to the earliest developmental processes in the human brain, scientists found that a group of genes critical for brain development is disrupted in Down syndrome.

Researchers from the University of Cambridge, University College London and the University of Wisconsin-Madison studied stem cells derived from Down syndrome fetuses and normal fetal tissue.

They discovered some of the key cellular and molecular processes that give rise to Down syndrome, one of the most common causes of developmental disability in humans.

The study, published in the Jan. 26 issue of the British medical journal The Lancet, is the first of its kind using human cells.

The key finding, according to Clive N. Svendsen, a UW-Madison professor of anatomy and neurology and a co-author of the report, is that a faulty genetic circuit results in dramatic changes in the development of the cells that make up the brain, which results in Down syndrome.

"These findings point to a serious deficit in specific genes known to be important for neuronal development," said Svendsen, director of the stem cell research program at the UW-Madison Waisman Center.

It has long been known that most instances of Down syndrome, which affects nearly 350,000 people in the United States alone, results from an extra chromosome, chromosome 21, in the cells of those who have the condition. However, the precise genetic events that lead to the abnormal brain development of people with Down syndrome have not been understood.

"Until now, we have only had mouse models of Down syndrome, which have not been so faithful in reproducing all aspects of Down syndrome (in humans)," Svendsen said.

"Now we have a complementary source of human stem cells with extra chromosome 21, and which can be grown indefinitely and used by a large number of scientists," he said.

Although the study's results are preliminary, identifying the abnormal brain development that gives rise to Down syndrome could ultimately lead to better treatments, including new drugs and, possibly, gene therapies, the researchers said.