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TARGET-DRIVEN DRUG DISCOVERY APPROACHES FOR REFRACTORY EPILEPSY

The human brain contains approximately 86 billion neurons containing classical neurotransmitters and neuropeptides. Glial cells are as abundant as neurons and are essential for a proper functioning of a healthy brain. Disruptions in this delicate interplay between nerve cells and glia are hallmarks of several brain diseases, including temporal lobe epilepsy (TLE), a frequent and drug-resistant form of epilepsy. TLE is also characterized by neuroinflammation, a complex process in which activated glia are known for releasing a myriad of pro- and anti-inflammatory cytokines, gliotransmitters, and other possible harmful (e.g. ROS) or protective (e.g. growth factors) molecules, thereby affecting epileptogenesis and disease progression.

We use well-established rodent models to unveil innovative future drug treatment strategies for refractory epilepsy. We have long standing expertise and continuous interest in studying molecular astroglial drug targets and neuropeptides. Our more classical pharmacological approaches have been expanded with state-of-the-art technologies such as photopharmacology. Moreover, with cell-type specific modulation via chemogenetics, an ideal marriage between gene therapy and pharmacology, we are investigating how glial cells signal to surrounding nerve cells and how they impact on ictogenesis.

Since epileptic discharges and seizures are frequent in Alzheimer’s disease patients, we are also studying the interplay between epileptic discharges and cognitive decline. In line with this hypothesis, we are investigating the potential use of antiseizure drugs as a possible treatment for Alzheimer’s disease.

Our ultimate goal is to translate our preclinical findings obtained at the bench into future clinical applications.

PI's

Ilse Smolders

Dimitri De Bundel

Ann Van Eeckhaut

C4N researchers

Surajit Sahu

Najat Aourz

Yana Van Den Herrewegen

An Buckinx

Maxime Vande Vyver

Amber Nous

Marie-laure Custers

Sofie Bournons

Liam Nestor