Target-driven drug discovery approaches for refractory epilepsy

PI: Ilse Smolders

 

C4N researchers:

Laura Walrave

Giulia Albertini

Yana Van den Herrewegen

An Buckinx

Najat Aourz

Jeanelle Portelli

 

The human brain contains approximately 86 billion neurons containing classical neurotransmitters and/or 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 acknowledged 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 want to unveil innovative future drug targets for refractory epilepsy patients by focusing mainly on non-synaptic modulation of epileptic phenomena in well-established rodent models for drug refractory epilepsy. The team has a continuous interest in extrasynaptic neuropeptidergic targets (e.g. ghrelin, angiotensins, neuromedins) as well as in molecular astroglial targets (e.g. connexin hemichannels, system xc-, …) known to interfere directly or indirectly with neuroinflammation. Moreover, with cell type specific approaches, such as chemogenetics, we are investigating how astrocytes can influence surrounding brain cells and how they can modulate ictogenesis and epileptogenesis. Our final goal is to translate these findings obtained at the bench into clinical applications. For that purpose, we use pharmacological ligands with translational potential.