Projektbeschreibung
Lichtaktivierte Wirkstoffe gegen Epilepsie
Die fokale Epilepsie ist eine neurologische Erkrankung, bei der spontane, übermäßige, unkontrollierte elektrische Signale in einem Teil des Gehirns abgegeben werden, was zu einem Krampfanfall führt. Bekannte pharmakologische Maßnahmen funktionieren nicht bei allen Betroffenen, und die Nebenwirkungen können mehrere Organe betreffen. Das Team des EU-finanzierten Projekts PhotoTherEpi schlägt zur Überwindung dieser Einschränkungen vor, Wirkstoffe zu entwickeln, die durch Lichteinstrahlung aktiviert werden (photoaktivierbare Wirkstoffe). Dafür testen sie verschiedene dieser Wirkstoffe in vitro und in einem Mäusemodell mit Epilepsie auf ihre antiepileptische Wirkung. Die Projektergebnisse könnten zu einer neuen Strategie zur Kontrolle der fokalen Epilepsie führen.
Ziel
As photo-activatable drugs (PDs) can be precisely controlled in space and time, caged and switchable photoactivatable drugs (CPDs, SPDs) are rapidly emerging as potential therapeutics for varied forms of cancer, vision loss, diabetes, or pain disorders. Despite their potential, PDs have not been exploited for epilepsy, a common, often debilitating neurological disorder. As 30% of epilepsies are medically intractable, and antiepileptic drugs often cause multi-organ side effects, PDs could break new therapeutic ground. PDs can be applied on demand, and locally activated/inactivated in single or multiple epileptic brain areas in a targeted fashion. This minimizes systemic side effects, and allows the application of potent drugs from other fields yet unthinkable in routine epileptology (e.g. general anesthetics). Importantly, being small molecules, different PDs can be combined or easily exchanged, and do not require protein expression. Using current and new PDs, we aim to control epileptic networks in vivo in a realistic epilepsy mouse model, and resected human brain tissue from patients with intractable epilepsy. Aim 1 will quantify antiepileptic potency of a range of PDs in human tissue using field potential and patch-clamp recordings, and cellular scale 2-photon imaging. In aim 2, PDs will be evaluated in vivo using wireless video-EEG, imaging and light-fiber-targeted drug photoactivation in chronically epileptic mice. Further, by use of caged immunomodulators, we will explore disease-modifying capacity of targeted PD photoactivation in epileptogenesis and chronic epilepsy. PhotoTherEpi will establish targeted photopharmacology as a versatile, and powerful new approach to control focal epilepsy, which could jumpstart a new branch of translational epilepsy research. The approach could obviate the need for resective surgery in many cases, and be used in multi-focal epilepsy. Importantly, it may be clinically tested in the foreseeable future.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
HORIZON-ERC - HORIZON ERC GrantsGastgebende Einrichtung
53127 Bonn
Deutschland