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Stem Cell Initiative
research briefs
A single gene on chromosome 21 may be implicated in some of the learning and cognitive disabilities characteristic of Down syndrome, Columbia researchers have found. The finding raises the prospects that a drug targeting the gene could improve memory abilities.
The idea of treating Down-related mental retardation with therapeutics has been all but unthinkable until recently. Down was considered too complex to treat because it is caused by an extra, third copy of chromosome 21, and numerous genes on the chromosome were believed to contribute to the disorder. Recent research, however, has suggested that learning and cognitive disabilities in Down syndrome may stem from only a handful of genes.
The new study, led by Gilbert Di Paolo, PhD, assistant professor of pathology, shows that one gene in particular – SYNJ1 – causes subtle biochemical changes in the brain’s neurons and learning deficits in mice with three copies of the gene.
“We’ve now come to a point where therapeutics for Down are seriously discussed at scientific conferences," Dr. Di Paolo says. "That is a huge change from the past and an encouraging sign for the future.”
PNAS 105(27): 9415-9420
Funders include NIH, Foundation Jerome Lejeure, National Down Syndrome Society, and the McKnight Foundation.
Cardiac Stents Impeded By Leptin
Clogged stents are twice as common in diabetic patients as in the general population, and a hormone released from fat, called leptin, may be partly responsible, according to new research led by Andrew Marks, MD, chair of physiology & cellular biophysics and Clyde and Helen Wu Professor of Molecular Cardiology, and Steven Marx, MD, associate professor of medicine and pharmacology.
The study found that leptin – at the elevated concentrations frequently found in patients with diabetes – stimulates the growth of cells responsible for clogging the stents, even in the presence of sirolimus, a drug used in many stents to prevent cell growth.
The same mouse study also identified a drug that counteracts the effect of leptin on cell growth. If added to current drug-eluting stents, such a drug may further reduce reclogging rates in patients with diabetes to the single digit rates seen in other patients.
About 250,000 Americans with diabetes receive drug-eluting stents every year. An improved stent would significantly reduce the numbers who eventually need coronary bypass surgery after their stents become severely obstructed.
PNAS 105(48): 19006-19011
The research was supported by the NIH and the American Heart Association.
Single Protein Can Initiate Stomach Cancer
A single inflammatory protein is enough to trigger the development of stomach cancer, a finding that shows inflammation has a more leading role in cancer formation than previously believed.
“For many years, inflammation was considered to promote the growth of tumors that already existed,” says the study’s senior author, Timothy Wang, MD, chief of digestive and liver diseases and Dorothy L. and Daniel H. Silberberg Professor of Medicine. “We now show that inflammation alone can initiate stomach cancer and that just one inflammatory molecule is sufficient.”
The study shows that excess amounts of an immune system protein called interleukin-1 beta (IL-1ß) – when present in the stomachs of mice – can start the inflammatory processes that ultimately lead to stomach cancer. IL-1ß, or the inflammatory cells they activate, could potentially prevent stomach cancer in people at high risk, Dr. Wang says.
Cancer Cell 14: 408-419
The study was supported by the NIH.
