ENDOGENOUS AED
Supply-rate depression as endogenous anti-epileptic mechanism
| Coordinatore | FYZIOLOGICKY USTAV AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE (VVI)
Organization address
address: VIDENSKA 1083 contact info |
| Nazionalità Coordinatore | Czech Republic [CZ] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2012-CIG |
| Funding Scheme | MC-CIG |
| Anno di inizio | 2012 |
| Periodo (anno-mese-giorno) | 2012-09-01 - 2017-08-24 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
FYZIOLOGICKY USTAV AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE (VVI)
Organization address
address: VIDENSKA 1083 contact info |
CZ (PRAHA 4) | coordinator | 0.00 |
| 2 |
FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Organization address
address: AVENIDA DE PIO XII 55 contact info |
ES (PAMPLONA) | participant | 100˙000.00 |
Mappa
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Obiettivo del progetto (Objective)
'Epilepsy is a prevalent neurological disorder affecting more than 1 % of all people, with the estimated number of 900,000 children and adolescents suffering from active epilepsy in Europe. Most current drugs targeting this disease have important adverse side-effects. An ideal drug would, however, potentiate the endogenous anti-seizure mechanisms that keep most humans epilepsy-free.
To date, these native “anti-seizure mechanisms” have not been identified. Recently, a novel candidate mechanism termed “supply-rate depression” was functionally characterized. It is only induced by excessive synaptic use, after which it dampens all pre-synaptic function for several minutes.
This proposal would test whether lowering the threshold for inducing supply-rate depression is protective against epilepsy using genetically engineered mice, and will additionally test a structure/function hypothesis related to the assembly of the vesicles in presynaptic terminal that could lead to a high-throughput drug screen.
These goals will be accomplished via the following Specific Aims: 1. To generate a synapsin 2 conditional knockout mouse line where synapsin 2 is deleted exclusively at excitatory synapses and thereby speed the onset of the protective mechanism at excitatory synapses. 2. To evaluate the susceptibility to seizures of the synapsin 2 conditional knockout mice using chemically induced models of epilepsy. 3. To apply state-of-the-art electron microscopy tomography techniques to test the structure/function hypothesis that the lengths of presynaptic vesicle tethering units are ~ 40% shorter in presynaptic terminals of synapsin 2 knockout synapses.
Results of this project may justify a large-scale industrial effort for developing a new generation of anti-epileptic drugs that target supply-rate depression. Thus, these new substances should have reduced occurrence and magnitude of unwanted side effects and would immensely improve the well-being of affected people.'