Description

Temporal lobe epilepsy (TLE) is an acquired form of epilepsy caused by various traumatic events. Presently available antiepileptic drugs do not adequately control seizures in one-third of patients and innovative treatment options are therefore necessary. TLE is associated with hippocampal cellular reorganizations leading to hyperexcitable neuronal networks, spontaneous epileptic seizures and severe comorbidities related to memory and mood. Astrocytes are active partners in synaptic transmission and regulation of memory and mood. Moreover, activated and proliferated astrocytes are a typical hallmark of TLE, and Ca2+-dependent glutamate release is a potential mechanism via which these astrocytes could contribute to neuronal hyperexcitability. I will validate a chemogenetic approach applying astrocyte-specific expression of genetically engineered receptors (DREADDs) that are exclusively activated by a designer drug to directly address the role of astrocyte signalling in TLE. I will also study whether chemogenetic modulation of the astrocytes affects the recurrence of spontaneous seizures and the associated comorbidities in a validated mouse model for TLE. The real benefit of such a chemogenetic future treatment would be that a designer drug can be administered systemically but will only affect the targeted DREADD-expressing astrocytes of the brain. This could potentially result in seizure suppression in patients that do not respond to classical anti-epileptic drugs.
AcronymFWOTM824
StatusActive
Effective start/end date1/10/1630/09/20

    Research areas

  • Epilepsy

    Flemish discipline codes

  • Pharmacology not elsewhere classified

ID: 25326782