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A cell (line) system for the evaluation of (new) anti-epileptic drugs especially suited for currently pharmacoresistant patients.

Projectomschrijving

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Samenvatting van de aanvraag

The aim of this project is to collect, organize and validate a cell line bank that expresses specific sodium channels and can be used for routine screening of (new) anti-epileptic drugs (AEDs). Sodium channels are responsible for the upstroke of the action potential and form the main target for classic as well as new anti-epileptic drugs, most of which affect synchronized neuronal firing by modulating the inactivation properties of the sodium channel. Most importantly they slow down recovery from inactivation, by binding to the inactivated state of the channel and so prevent high frequency firing and synchronization. Our previous and ongoing scientific work has demonstrated that AEDs differ in their relative affinity for distinct sodium channel subtypes. As sodium channel expression is age and state dependent, this could be an explanation for the often occuring build up of pharmacoresistance in patients(ultimately about 30% of all epilepsy patients!). Currently we have labour and animal intensive models to test these properties, but an adequate bank that contains the most important variations and in particularly their pharmacological profile against current drugs, would be enormously helpful and reduce the need for epileptic animals considerably. Our proposed characterized and validated HEK cell line bank will facilitate screening of current AEDs (and the investigation of drug interactions) and create screening possibilities for new AEDs. It will also bring personal medicine for rare but severe forms of epilepsy, related to sodium channel mutatations within reach, without the need for large amounts of new animal research.

Onderwerpen

Kenmerken

Projectnummer:
114000091
Looptijd: 100%
Looptijd: 100 %
2010
2015
Onderdeel van programma:
Projectleider en penvoerder:
Prof. dr. W.J. Wadman
Verantwoordelijke organisatie:
Universiteit van Amsterdam