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THURSDAY, Oct. 2 (HealthDay News) -- An animal study raises a warning sign that a new class of drugs that shows promise against a variety of ailments ranging from cancer to Alzheimer's disease might cause congenital heart defects, researchers report.
"We have no idea if there will be any risk, but the study suggests we should be aware of the possibility," said Dr. Thomas Force, a professor of medicine at Thomas Jefferson University in Philadelphia and lead author of an online report in the October issue of the Journal of Clinical Investigation.
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The drugs are aimed at a gene that produces a protein called glycogen synthase kinase-3 (GSK-3). The only drug now on the market that targets GSK-3 is lithium, given to treat bipolar disorder. It is a relatively weak GSK-3 inhibitor. Because of the wide range of GSK-3 protein activity, there is active research on molecules that inhibit that activity.
The study was done on mice bred to lack two forms of the gene, GSK-3-alpha and GSK-3-beta. Mice lacking GSK-3-alpha were born with normal hearts, but those lacking GSK-3-beta all died before birth. Some died halfway through gestation of severe liver degeneration. Most died at a later stage of development, with numerous heart defects, including abnormally thick heart muscle caused by overgrowth of the muscle cells.
"It has been suggested in the past that lithium might cause birth defects," Force said. "It is not clear whether that is the case. The data from our paper suggest that newer agents with much more potent GSK-3 inhibitory action could raise the level of danger."
It is difficult to get detailed information on the development of new GSK-3 inhibitors, because drug companies try to keep that information to themselves, Force said. "These are proprietary compounds, so they are not talking about what they are doing," he explained.
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