Project description
Light-activated drugs against epilepsy
Focal epilepsy is a neurological condition associated with the firing of sudden, excessive, uncontrolled electrical signals in one part of the brain known as seizures. Existing pharmacological interventions do not work for all patients and may cause multi-organ side effects. To overcome these limitations, scientists of the EU-funded PhotoTherEpi project propose to develop drugs that become activated upon light administration (photoactivatable drugs – PDs). The work involves the screening of various PDs in vitro and in a mouse model of epilepsy for their anti-epileptic effect. Project results may unveil a novel strategy for controlling focal epilepsy.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
53127 Bonn
Germany