Newswise — DALLAS (SMU) – An estimated 50 million people worldwide have epilepsy, making them 16 times more likely to die suddenly compared to the general population. SMU biology researcher Edward Glasscock has received a 5-year, $3 million grant from the National Institutes of Health for a study that he hopes will lead to the identification of biomarkers to help identify people at risk for sudden unexpected death in epilepsy, known as SUDEP.
What causes sudden death in people with epilepsy is largely unknown, making it difficult for clinicians and researchers to predict who is most at risk. However, one popular theory is that seizures initiate faulty electrochemical signals in brain regions that control the heart and breathing, causing miscommunication between the brain, heart, and lungs leading to respiratory failure or heart arrhythmias. If the patterns of this faulty inter-organ crosstalk could be identified in people with epilepsy, then it could serve as an indicator for who is most at risk for sudden death, as well as lead to the development of new treatments to prevent SUDEP.
Glasscock, associate professor of biological sciences at SMU (Southern Methodist University) is working in collaboration with Leonidas Iasemidis, of the Barrow Neurological Institute in Phoenix, to investigate how these faulty electrochemical signals affect the brain-heart-lung pathways. Glasscock and Iasemidis are using a multidisciplinary bioengineering systems approach that would not only identify biomarkers but also provide insight on the biological basis of SUDEP, which can lead to better targeted therapies.
Studying epilepsy and SUDEP can lead to individualized support
Epilepsy, with new cases often diagnosed in young children, occurs because of abnormal electrical activity in the brain that causes seizures. Because there are many different causes and types of epilepsy, it is described as a spectrum disorder, which makes it difficult to study. However, scientists have made strides in discerning the genetic factors and mechanisms that cause some people to develop epilepsy.
In the body, electrochemical signals are related to chemical ion gradients, like potassium or sodium. Cells allow these ions to pass into and out of the cell membrane through channels. These channels are highly regulated because too few or too many of the ions can cause problems with the brain’s signaling pathways. It is thought that one cause of epilepsy is related to genetic mutations that cause these ion channel regulators to malfunction. This results in abnormal interactions between the brain, heart, and lungs, which in turn may cause sudden death.
The Glasscock Lab in SMU’s Dedman College of Humanities and Sciences is focused on understanding the genes and mechanisms underlying epilepsy and SUDEP. However, SUDEP is difficult to study in humans because it occurs suddenly and unexpectedly, meaning there is no way to know which individuals with epilepsy to monitor. And, SUDEP only occurs in a small number of cases, making it difficult to find patterns in the population. For these reasons, the Glasscock lab, uses mouse models as an alternative to studying sudden death in humans.
The NIH grant is for a project that builds on previous research Glasscock and Iasemidis have published in the IEEE Open Journal of Engineering in Medicine and Biology on their bioengineering systems approach for understanding the interactions between the brain, heart, and lungs and how they change with seizures. For this new project, they will look at mice with mutations that disrupt the electrochemical signals in brain cells to see if these changes provide patterns of brain-heart-lung dysfunction that can be used as clues to identify when sudden death may occur.
The Glasscock/Iasemidis research is supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01NS129643. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. – Heather Zeiger
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