Description du projet
Des médicaments activés par la lumière contre l’épilepsie
L’épilepsie focale est une affection neurologique associée à l’émission de signaux électriques soudains, excessifs et incontrôlés dans une partie du cerveau, appelés «crises». Les interventions pharmacologiques existantes ne fonctionnent pas pour tous les patients et peuvent provoquer des effets secondaires sur plusieurs organes. Pour surmonter ces limites, les scientifiques du projet PhotoTherEpi, financé par l’UE, proposent de mettre au point des médicaments qui s’activent à la lumière (médicaments photoactivables ou MP). Les travaux portent sur le criblage de divers MP in vitro et dans un modèle d’épilepsie murin, afin de déterminer leur effet antiépileptique. Les résultats du projet pourraient révéler une nouvelle stratégie pour contrôler l’épilepsie focale.
Objectif
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.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
53127 Bonn
Allemagne