Where We Are in the Search For a Cure
An Interview with John Swann, PhD
Dr. Swann is Professor of Pediatrics and Neuroscience at Baylor College of Medicine in Houston, TX. He served as President of the American Epilepsy Society in 2007, and co-authored the paper regarding the Epilepsy Benchmarks, “Curing Epilepsy: Progress and Future Directions.”
What are the NIH Epilepsy Research Benchmarks?
The Epilepsy Benchmarks are research goals established by the epilepsy research community in collaboration with the National Institute for Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH). The Benchmarks were developed after a White House-initiated, CURE co-sponsored NIH conference in 2000, and updated following a second NIH conference in 2007. They are compre¬hensive and ambitious research goals deemed achievable over the next decade and aimed at finding cures.
How have the Epilepsy Benchmarks changed the way research is being done?
Researchers have embraced the Benchmarks, and many have chosen one or more as areas of investigation. The Bench¬marks foster discussion of new observations between clinicians and researchers, and encourage cross-fertilization with other scientific disciplines. They are particularly helpful to young investigators, outlining the breadth of topics that are open for exploration and discovery.
What are the two major breakthroughs in epilepsy research in the past decade?
The biggest breakthrough has been the identification of genes involved in normal brain function, which when they mutate, produce epilepsy. At least eleven epilepsy genes have been identified in humans, and more than 50 in mice. Mouse models of human epilepsy with specific gene mutations allow researchers to study genetic causes of epilepsy, and serve as important resources for developing and testing new therapies.
Great strides have also been made in identifying the numerouschanges in nerve cells that occur in the process of epileptogenesis—the process by which a normal brain begins to produce seizures—so that they can be therapeutically targeted to prevent the development of epilepsy.
What do you see as promising areas that will yield advancements in the coming years?
Scientists are turning their attention to co-morbidities of epilepsy, one of the three major subtopics in the Epilepsy Bench¬marks. More than the general population, people with seizures face difficulties in learning and memory as well as psychological problems such as depression and anxiety. Improved understand¬ing of why this occurs will help unlock ways to predict, treat, and cure these patients.
Has there been an increase in the amount of funding for epilepsy research?
In the US, most funding comes from the NIH. Between 1995 and 2003, their budget doubled and this increase helped to boost our understanding of the brain. For instance, we learned about the molecular makeup of individual nerve cells and the synaptic connections between them. The molecular machines within these connections, which are composed of hundreds of molecules, operate in coordinated and efficient ways and allow communica¬tion between nerve cells. We are finally beginning to understand how alterations in some of these molecules cause these machines to become less efficient or to work in unusual ways to produce seizures and even to impair learning and memory.
But, between 2003 and 2009, when research funding failed to keep up with inflation, there was an enormous negative impact on research. The recent influx of stimulus funding committed to research over the next two years will hopefully benefit epilepsy research, but the future after that is difficult to predict.
This is why CURE is so important. Research funded by CURE has unquestionably had a major impact on epilepsy research, particularly in helping new investigators get started in this field, and helping senior investigators start new projects that can grow and compete for support from the NIH. These are the scientists who will discover the next epilepsy gene, unravel the alterations in molecular machines that produce epilepsy, discover new therapies, and pave the road to a cure.
To read the NIH Epilepsy Benchmarks, please visit: www.ninds.nih.gov/research/epilepsyweb/2007_benchmarks.htm
An Interview with Jeff Noebels, MD, PhD
Dr. Noebels serves on CURE’s Scientific Advisory Board. He is Professor of Neurology, Neuroscience, and Molecular and Human Genetics at Baylor College of Medicine in Houston, TX.
Tell us a little about yourself and how you became interested in epilepsy research.
I was fortunate to join the laboratory of David Prince at Stanford University, a world leader in training and launching young epileptologists. I realized I could hardly commit my life to the riddle of epilepsy without understanding the clinical disorder, and decided to go to medical school to become a neurologist. For 20 years, I have been training scientists and neurologists to consider DNA when they see a patient with seizures. Every day, we look for new molecular and cellular troublemakers in the clinic and laboratory, and search for better ways to prevent or reform them.
What progress have we seen in epilepsy research over the past ten years?
The field of epilepsy research is vibrant and has made great strides in three key areas that improve the care of patients with epilepsy. First, detecting sites of abnormality by brain scanning is greatly enhanced; we now have stronger magnets, more pixels, faster image analysis, and astonishing 3-dimensional software. The second area is in genetics, which has revealed the striking diversity of inherited errors in genes that lead to the risk of seizures. Gene tests also promise to explain why some drugs are effective in certain individuals and not in others. Finally, biotechnology and bioengineering approaches in the laboratory are revolutionizing the ways we can modify the activity of very specific circuits in the brain.
What do you see as the most promising advances in the field?
The development of safe and ‘smart’ molecular probes that could be administered to a patient orally or by injection before a brain scan is very exciting. These probes, already on the drawing board, illuminate the specific brain networks involved in a seizure, even if it occurred a day or even a week earlier and could make an enormous difference in improving the speed and accuracy of clinical diagnosis. Other probes for molecules that transmit chemical signals between cells may also help pinpoint which class of drug to try first. Combining this information with gene testing will enable us to take a giant step forward in the treatment of epilepsy.
What is the single largest obstacle to finding a cure?
The major obstacle is raising and directing the necessary resources to both attract talented young researchers to the field of epilepsy and to support all of the critically needed basic research that is on the verge of leading to real breakthroughs. The number of patients affected and the severity of the problem calls for more support directed toward epilepsy research—both from the government and from private foundations like CURE. With a more appropriate infusion of funding, we will be able to unlock the mysteries of epilepsy and offer our patients the long overdue solutions they deserve.