With the help of neural stem cells and UW-Madison research, scientists are one step closer to understanding Down syndrome, one of the most common causes of developmental disabilities.
Scientists described a new model to study Down syndrome and identified two defective genes found in diseased cells in a recent issue of The Lancet, a British medical journal.
Clive Svendsen, UW anatomy and neurology professor and director of the stem-cell research program at the Waisman Center, co-authored the paper with a team of scientists from the University of Cambridge and University College in London.
Approximately 5,000 children are born with Down syndrome every year in the United States, making it one of the most common birth defects.
Down syndrome, also called trisomy 21, occurs when one’s cells have three copies of chromosome 21 instead of the normal two found in healthy individuals.
Though scientists have known the cause of Down syndrome for over 30 years, little was known about why the extra chromosome led to developmental defects.
That has changed with the recent identification of two defective genes in Down syndrome patients.
“There are two essential genes in the Downs that hadn’t been found previously. They have to do with the development of the nervous system,” Svendsen said. “These stem cells only made about 20 percent of normal neurons — not very efficient.”
This was the first study that used human cells to study the disease. Previously, scientists had to rely on an animal model.
Though the mouse model will still play an important role in studying the disease, mice have different genes and chromosomes than humans. Since mouse and human Down syndrome are not exactly alike, there may be different cellular pathways involved. These differences mean scientists can only make analogies between the mouse and human disease.
Scientists can now study the human version of Down syndrome directly.
“It allows you to go straight to the heart of the matter to see what’s happening in cells with this genetic disease,” said Ronald Kalil, professor of ophthalmology and visual sciences and director of the W.M. Keck Laboratory for Biological Imaging.
Neural stem cells were collected from Down syndrome patients and induced to grow neurons in culture. The neurons from the defective stem cells were shorter, misshapen and less frequent when compared to the control.
The human neural stem cells will also provide an ideal medium to test drugs and other treatments that may help neurons develop normally.
“By understanding how the disease process works, it can at least give you a handle on how to produce a treatment,” Svendsen said.
Traditionally stem cells are discussed as possible therapies, but using them to study Down syndrome and other genetic diseases will allow scientists to have a more accurate understanding of what is occurring.
“There are probably other genetic diseases that aren’t as predictable as Down syndrome that would also be amenable to this sort of approach,” Kalil said.
