|Epilepsy Research Benchmarks|
| The 2007 Epilepsy Research Benchmarks are now available
|Judith Hoyer Lecture on Epilepsy|
|Anticonvulsant Screening Program (ASP)
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|Brandy Fureman, Ph.D.
Program Director, Channels Synapses & Circuits Cluster
Epilepsy Benchmark IIIA
Benchmark Area III. Create and implement new therapies free of side effects that are aimed at the cessation of seizures in patients with epilepsy.
A. Specific Benchmark: Assess the potential efficacy of therapies in individual patients by examining effects on markers of epileptogenicity. Aim at developing highly individualized treatments that take into account the maturational state of the brain and other factors proven to be relevant such as hormonal status.
2005 Report submitted by Benchmark Steward(s):
Tallie Z. Baram, M.D., Ph.D. (University of California, Irvine)
Background of the benchmark goal:
Age and individual ‘environmental’ differences: stress, gender, and the hormonal underpinnings of both. These two factors affect the likelihood of seizures and the response to seizure medications. Therefore, to provide therapies that will be tailor-made to a given individual, we need to consider all of these factors.
Current status of the field:
It is now recognized that effective therapies need to take into account the age-specific processes described above. In other words, to be effective, therapies for epilepsies during development will need to be designed to account for the different underlying mechanisms of the disease, as well as the age-specific handling and reactions to the therapeutic agents.
It is recognized that sex, sex hormones and stress hormones all influence the process by which epilepsy arises, the type of the epilepsy and the way the individual responds to medication. To be effective, therapies need to take these facts into consideration.
“Assess the potential efficacy of therapies in individual patients by examining effects on markers of epileptogenicity”
A. The human study of Van-Landingham (Ann Neurol, 1998), suggesting that Magnetic Resonance Imaging (MRI) changes might provide a marker for Epileptogenicity has been corroborated in a larger British study (Scott et al., Brain, 2002,3)
B. Significant progress has been achieved in defining MRI as marker of Epileptogenicity in a developmental epilepsy model, that leads to TLE: MRI changes have been identified in prospective analysis of limbic structures including hippocampus. In the animal model, pre-existing malformations, lesions or other factors that might lead to MRI changes can be excluded, by imaging all subjects also before the inciting epileptogenic event. (Dube et al., Ann Neurol, 2004)
C. Several proposals for anti-epileptogenesis model validation have recently been funded.
D. A major human study fully launched: a prospective evaluation of MRI as marker for epileptogenesis (Shinnar).
E. Meetings and Education (partial):
“Aim at developing highly individualized treatments that take into account the maturational state of the brain and other factors proven to be relevant such as hormonal status”.
A. Use of functional MRI as marker of gender-dependent and individual outcome to surgical treatment of Epilepsy (Rabin et al., Brain 2004)
B. Identification of gender specific side-effects of currently available AEDs (Human: Herzog et al., Epilepsia, 2004; Animal: Tauball et al., Epilepsia 2003).
C. An ongoing, prospective assessment of the role of individual and genetic factors in the response to specific anti-epilepsy drugs (Glauser)
D. CRISP search suggests 26 new grants (R21, K08, RO1 etc), pertaining to this benchmark.
Top priorities for next 5-10 years:
Roadblocks to progress:
Last updated January 12, 2010