Possible Therapeutic Target for Mysterious Brain Blood-vessel Disorder

Abnormal, leak-prone sproutings of blood vessels in the brain, called cerebral cavernous malformations (CCMs), can lead to seizures, strokes, hemorrhages and other serious conditions, yet their precise molecular cause has never been determined. However, cardiovascular scientists at the Perelman School of Medicine at the University of Pennsylvania have studied this pathway in heart development and discovered an important set of molecular signals, triggered by CCM-linked gene defects that could potentially be targeted to treat the disorder. Although CCMs have a relatively high prevalence (1 in 200), they typically go undiagnosed until symptoms arise and can only be treated by brain surgery. Research on CCMs has been slowed by the difficulty of recreating the disease in lab animals. Previous studies have shown that CCM genes remain lethal to fetal mice, even when they are limited to the endothelial cells that line blood vessels and the heart. In the new study, researchers used advanced techniques to restrict CCM gene disruption to the endothelial cells of the developing heart, leaving the mouse vascular system to develop otherwise normally. The resulting mice still died before birth, this time from a failure of normal heart development, which is not seen in human CCM patients. However, the mice survived in the womb about one week longer than before, allowing the researchers to learn more about the effects of the gene disruptions, and ultimately to find a previously unknown CCM-related signaling pathway. To read more about this study, click here.