Brain arteriovenous malformations (bAVMs) are abnormal connections of arteries and veins in the brain that form a tangled web of vessels instead of a normal capillary network. bAVMs occur in about one in 2,000–5,000 people. They represent the main cause of hemorrhagic stroke in young patients with other complications, such as focal or generalized seizures, localized headache, and difficulty with movement, speech, and vision. Treatment of bAVM has been limited and mainly relies on surgical resection, gamma knife or endovascular embolization to eliminate bAVM. These treatments are typically limited by the location of the AVMs in the brain and many patients with bAVM have been left untreated, unable to be treated, incompletely treated, or incompletely treated with complications. Unfortunately, all of these patients remain at risk of a brain hemorrhage due to a rupture during their lifetime. If the bAVMs do not result in premature death, the physical and psychological impacts significantly interfere with their quality of life. Although the bAVMs are usually congenital, meaning someone is born with one, they are not inherited suggesting the involvement of non-inheritable factor(s). We are currently interested in the role of soluble endoglin, vascular endothelial growth factor, and somatic mutation of RAS genes based on clinical and pre-clinical evidence demonstrating their involvement in bAVM. By manipulating these factors individually, we have successfully established an animal model of a bAVM and are now actively addressing the underlying mechanisms using the models. In addition, we are collecting human bAVM samples that will be utilized for gene/protein profiling. We expect that the human data will give us critical insight into the molecular mechanisms of bAVM pathophysiology when compared with the pre-clinical studies. For the projects, we are collaborating with labs at Barrow Neurological Institute (Phoenix, AZ) and Universität zu Lübeck in Germany, and the results have been presented in several international conferences, such as the 2018 Society for Neuroscience (San Diego, CA) and the 2019 AHA Vascular Discovery Meeting (Boston, MA). Our research has been published in the Annals of Neurology in May 2021 and we are currently preparing grant proposals with hypotheses based on the collected preliminary data. Our ultimate goal is to develop therapeutic strategies for bAVM patients. This will be accomplished by completing several steps, including finding targets, developing a strategy to regulate the targets, and validating the efficacy and safety of the methods in animal models and humans, and, most importantly, by your support.
Written by Dr. Eunhee Kim
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