COLUMBUS, Ohio Conventional wisdom among scientists for years has suggested that because individuals with Down syndrome have an extra chromosome, the disorder most likely results from the presence of too many genes or proteins contained in that additional structure.
But a recent study reveals that just the opposite could be true that a deficiency of a protein in the brain of Down syndrome patients could contribute to the cognitive impairment and congenital heart defects that characterize the syndrome.
Scientists have shown in a series of experiments that there are lower levels of this protein in the brains of humans and mice with Down syndrome than are present in humans and mice without the disorder.
The researchers also showed that manually manipulating pieces of RNA that regulate the protein could increase protein levels in both human cell lines and mouse brains. In fact, an experimental drug that acts on those RNA segments returned this protein to normal levels in mice that model the syndrome.
When this RNA segment is overexpressed meaning that more of it is present than needed in a cell the protein level goes down, or is underexpressed. A total of at least five of these RNA segments are naturally overexpressed in persons with Down syndrome because the segments are housed on chromosome 21 the chromosome that causes the disorder.
"We're talking about a paradigm-shifting idea that maybe we should look for underexpressed proteins and not overexpressed proteins in Down syndrome," said Terry Elton, senior author of the study and a professor of pharmacology at Ohio State University.
"What this offers to the Down syndrome community is the potential for at least five new therapeutic targets to pursue."
The Centers for Disease Control and Prevention estimates that about 13 of every 10,000 babies born in the United States each year have Down syndrome, characterized primarily by a mild-to-moderate r
|Contact: Terry Elton|
Ohio State University