Unlocking the Mysteries of Epilepsy
Despite all of the medical and technological advances, the human brain continues to be a mystery. Revealing answers about one of the most common neurological diagnoses – epilepsy – is the goal of a husband and wife research team at Creighton University.
Tim and Kristina Simeone, assistant professors of pharmacology, are studying a special high-fat diet – called the ketogenic diet – which has been found to be effective in controlling seizures in patients who don’t respond to currently available medications.
While the scientific community has long recognized the astonishing therapeutic effects of the ketogenic diet, the Simeones aim to find out how the diet affects the brain in ways current medication does not.
“We are using the ketogenic diet as a key to unlock the mystery behind epilepsy and its spectrum of associated disorders,” Kristina said.
The Research Couple
Tim and Kristina met while completing research at University of California Irvine under Tallie Baram, M.D., Ph.D., who is credited with several groundbreaking studies in pediatric neuroscience. Tim studied febrile seizures at the postdoctoral level, while Kristina was focused on her doctoral research into early-life stress.
The couple then moved to Phoenix for postdoctoral research at the Barrow Neurological Institute at St. Joseph’s Hospital – turning their attention to understanding epilepsy and the effects of the ketogenic diet.
They were the first researchers to use a novel technology to look at network activity within resected human epileptic tissue, which illustrated the importance of viewing epilepsy and therapeutics from a network vantage point.
Coming to Creighton
Since joining the faculty at Creighton in 2009, both Tim and Kristina have maintained this research, but from their own unique perspectives.
Tim continues to examine seizures from the network vantage, using electrophysiological techniques to see how the neuronal and glial cells act in concert to generate the oscillations or “brain waves” that underlie cognitive and behavioral outputs of the brain. It’s thought that seizures represent oscillatory behavior in disarray.
Kristina approaches the research from her view as a neuroanatomist and neurobiologist. Through a research grant, she is working to understand the mechanism responsible for sleep disorder co-morbidities associated with epilepsy.
She is also interested in brain metabolism – how the brain processes and uses energy and how that differs in epilepsy. This spring, Kristina submitted a patent application for a novel treatment that targets the mitochondria to reduce seizure frequency, intensity and neural damage caused by seizure; it also can be used as a neuroprotective agent.
A New Collaboration
Despite their differences in approach, the Simeones’ combined interests and expertise allow them to research epilepsy from the disease state down to the molecular level, including:
- In vivo EEG seizures in mice: How do drugs and novel treatments influence seizures?
- In vitro slices: How do drugs influence different parts of the seizure in a slice?
- Brain biogenetics: How do live mitochondria function in epileptic brain regions?
- Molecules: What proteins are changed in the epileptic brain as compared to a healthy brain?
- And, how does the ketogenic diet restore brain homeostasis?
The Simeones are especially excited about a new collaboration with Jiri Adamec, Ph.D., professor of biochemistry at the University of Nebraska-Lincoln’s Redox Biology Center, to assess how epilepsy and the ketogenic diet effect brain metabolism using novel metabolomic, lipidomic and proteomic technologies.
“Jiri has already found intriguing differences that are changing the way we think about this disorder,” said Kristina.
So where does the future lie for the Simeones? They believe there will be a discovery that will lead to life-changing treatment opportunities for people living with epilepsy.
“Even the best medications we have today are merely symptomatic – they are not a cure,” Tim said, with the caveat that there is no general consensus on what constitutes a “cure” for epilepsy.
“But I believe we are on our way to identifying a common denominator that will better address the underlying cause of this disease, as well as multiple other neurological disorders.”