The field of epilepsy research has undergone a dramatic transformation in the past decade. However, substantial gaps exist in our understanding of epilepsy, from its causes and prevention to its clinical impact and treatment. In March 2000, prominent epilepsy research scientists, health care providers, and leaders of epilepsy organizations came together for a seminal conference to discuss what it would take to reach a cure for epilepsy, defined as the prevention of epilepsy in people at risk, and by effective and safe therapy (“no seizures, no side effects”) for those with the disorder. Cosponsored by the National Institute of Neurological Disorders and Stroke (NINDS), the American Epilepsy Society, Citizens United for Research in Epilepsy, the Epilepsy Foundation, and the National Association of Epilepsy Centers, this White House–initiated conference highlighted advances in neuroscience, imaging, genetics, and clinical research related to mechanisms of epileptogenesis, and emphasized the vital need for further research that would lead to new treatments and cures.
Participants were eager to identify a way to evaluate progress resulting from this historic event, and a session was added to the conference to “benchmark” the outcomes. The NINDS subsequently worked with more than a dozen Epilepsy Research Stewards—established leaders in the field of epilepsy research—to define a series of goals for the field that could serve as a research agenda. The NINDS and the Stewards developed a series of Epilepsy Research Benchmarks based on the three major topic areas of the 2000 Conference: (1) interrupting and monitoring epileptogenesis; (2) genetic strategies; and (3) developing new therapies. The first of these Benchmarks entailed goals that would hasten progress toward understanding the fundamental causes of epilepsy at the anatomic, physiologic, and genetic/molecular levels; and defining markers of epileptogenicity. This Benchmark also encouraged the validation and use of improved animal models for therapeutics testing. The second Benchmark focused on prevention through the use of epileptogenicity markers to identify tissue targets for preventive therapies, and the completion of large clinical trials of neuroprotective or antiepileptogenic compounds in high-risk individuals. The third Benchmark highlighted the development of improved therapies. Markers of epileptogenicity were again emphasized, in this case for the efficacy testing of therapeutics. Other factors were recognized as important for improved personalization of therapies, including an individual’s developmental stage, hormonal status, and genetic profile. Multiple treatment strategies were encouraged, including the continued refinement of bio-sensors and seizure suppression systems, new approaches for epilepsy surgery, and novel therapies such as cell transplants or vaccines. This Benchmark also called for the achievement of a complete cure for a form of genetic epilepsy through appropriate translation through preclinical research studies. A complete list of the original Epilepsy Research Benchmarks is available at: http://www.ninds.nih.gov/funding/research/epilepsy-web/epilepsybenchmarks.htm. Over the subsequent 5 years, the research community made substantial progress on these Benchmarks, including but not limited to advances such as:
- Improvements in neurotransmitter imaging through the development of magnetized nanoparticles.
- The development of a collaborative project to understand changes in gene expression associated with epileptogenesis in different animal models.
- The establishment of a database that enables researchers to search nonproprietary structural and biologic data on anticonvulsant drugs.
- The initiation of clinical trials designed to prevent the development of epilepsy after brain injury.
- An improved understanding of both age and hormonal influences on the underlying cellular mechanisms of epilepsy.
- New discoveries related to epilepsy pharmacogenetics/pharmacogenomics.
- Progress in seizure detection and brain stimulation to control epilepsy, as well as other surgical approaches to treatment.
- The development of the Epilepsy Phenome/Genome Project to facilitate the discovery of genes responsible for more common forms of epilepsy.
These and other advances associated with the original Benchmarks—as well as roadblocks to progress in some Benchmark areas—are detailed in a series of reports available at: http://www.ninds.nih.gov/funding/research/epilepsyweb/epilepsybenchmarks.htm.
As these reports illustrate, research goals are never static, and the evolving needs of the research community, along with the increasing recognition that the comorbidities of epilepsy present a significant challenge to the goal of “no seizures, no side effects,” strongly indicated that a reassessment of the Benchmarks was warranted.
In March 2007, this reassessment took place, with more than 400 researchers, physicians, patients, family members, and epilepsy organization leaders convening on the National Institutes of Health campus to participate in the “Curing Epilepsy 2007: Translating Discoveries into Therapies” Conference. Organized by the NINDS in collaboration with epilepsy research and voluntary organizations, the meeting was a follow-up to the successful conference in 2000. Participants reviewed the original Epilepsy Research Benchmarks and prioritized topic areas felt to be most promising, as well as those in need of attention. The NINDS solicited public input on these changes to the Benchmarks, and the Epilepsy Benchmark Stewards gathered in October 2007 to discuss the input received and to finalize the new set of goals, outlined below and available (along with the specific Stewards who contributed to each of these goals) at: http://www.ninds.nih.gov/funding/research/epilepsyweb/2007_benchmarks.htm.