NIH Funds Research Into Sudden Unexpected Deaths in Epilepsy

Pauline Anderson

December 18, 2014

SEATTLE, Washington — To address what experts call a "frightening mystery," the National Institutes of Health (NIH) is pledging $5.9 million in funding for research into sudden unexpected death in epilepsy (SUDEP).

The funds, announced at the recent American Epilepsy Society (AES) 68th Annual Meeting, will go mostly toward investigator-initiated studies, including many in the area of genetics, said Walter Koroshetz, MD, acting director, National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH.

Dubbed the second "Center Without Walls," the new program aims to "bridge science and clinical medicine," said Jeffrey Noebels, MD, PhD, professor, neurology, neuroscience, and molecular and human genetics, Baylor College of Medicine, Houston, Texas, during a press briefing announcing the funding.

In 2010, NINDS established the first "Center Without Walls" to address challenges and gaps in epilepsy research. That program encourages sharing of data between researchers from various disciplines and institutions.

Leading Cause of Death

SUDEP is the leading cause of death in patients with epilepsy. "SUDEP is not common, but it's fatal and scary and affects 1 in 1000 people with epilepsy," said Dr Koroshetz.

That translates into up to 3000 people in the United States each year. Victims of are often young — between 20 and 40 years. There are no firm causes and no confirmed strategies to prevent it.

The hope, said Dr Noebels, is that the new program will "uncover the mysteries" of SUDEP, to help in the understanding of "when it happens and who it happens to" and to make progress in terms of treatments.

The ambitious program will create a network of clinical sites that will use input from engineering, informatics, and other experts to carry out various aspects of research. Some laboratory scientists will study tissue and brain samples of SUDEP victims. Others will use imaging and perform molecular autopsies "to identify genetic culprits," said Dr Noebels.

Yet other scientists, he said, will use sophisticated approaches to investigate animal models in the hunt for a genetic defect. "They will use exquisite single cell analyses to trace cellular expression of the disorder and to test medicines."

The molecular genetics diagnostic arm of the project will look at how patterns of genes may put some patients at risk but possibly protect others.

As the link between cardiac conditions and SUDEP becomes increasingly clear, the project "highlights the important relationships" between epilepsy and cardiology experts, noted Dr Noebels.

Patients who die of SUDEP often do so at night while asleep. The prone position, therefore, appears to be important. These victims often had experienced epilepsy for many years and had intractable seizures.

There's also a growing interest in a possible relationship between SUDEP and sudden infant death syndrome (SIDS). The "Back to Sleep Program" (also called the "Safe to Sleep" campaign) in which parents are encouraged to put their babies to sleep on their backs, has reduced mortality by 50%, Dr Noebels pointed out.

The projects funded and principle investigators are the following:

  • Samden Lhatoo, MD, Case Western Reserve University, Cleveland, will head a team that will examine ways in which changes in brain structure are linked to abnormal physiologic responses and altered breathing patterns that occur during seizures.

  • A team headed by Maria Thom, MD, University College London, and Orrin Devinsky, MD, New York University, New York, will look at the role of the chemicals adenosine and serotonin in SUDEP, using the world's largest collection of brains from people with epilepsy who died unexpectedly and from tissues of patients undergoing epilepsy surgery.

  • Researchers led by Alica M. Goldman, MD, PhD, Baylor College of Medicine, will focus on changes in the size and structure of the brain and brainstem from SUDEP victims.

  • Another team at Baylor, led by Dr. Goldman and John William Belmont, MD, PhD, will attempt to identify genes that cause SUDEP and develop tools to predict who is at risk.

  • A laboratory at the University of Iowa, headed by George B. Richerson, MD, PhD, will investigate the role of dysfunction in brainstem pathways involved in controlling breathing and look for relevant biomarkers.

  • Jack M. Parent, MD, and Lori Isom, PhD, University of Michigan, Ann Arbor, will use mouse models and stem cells from patients with Dravet syndrome, a severe form of pediatric epilepsy that carries a high SUDEP risk, to examine changes in neuronal function and heart rhythm that may contribute to SUDEP.

  • Changes in genes that cause abnormalities in heart rate and breathing patterns is the topic of research to be carried out by Dr Noebels at Baylor College and his colleagues. The aim is to identify genes and test candidate drugs.

  • At Case Western Reserve University, Guo-Qiang Zhang, PhD, and his team will research ways to share data and resources across institutions involved in the Center Without Walls.

  • Dr Lhatoo at Case Western, along with Dr Noebels at Baylor will oversee, facilitate, and prioritize the research at the various centers.

American Epilepsy Society (AES) 68th Annual Meeting. Announced December 8, 2014.

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