Current drug discovery is dominated by target-based approaches, usually cell-based assay, which seek to identify compounds that modify in vitro activity of a specific protein target. Since in many cases they fail to capture the complexity of the vertebrate nervous system, there is an increasing need for in vivo model organisms allowing for HTS of large numbers of small molecules and also target validation. Zebrafish (Danio rerio) are an invaluable model in the field of neuroactive drug discovery because they unifying drug discovery- and target-related work in relevant in vivo whole organism conditions.
At the Laboratory for Molecular Biodiscovery at KU Leuven we established a zebrafish platform for drug discovery and target validation for epilepsy. We have several in-house validated chemical and genetic models of seizures and epilepsy. In order to study the epilepsy phenotype, we employ specialized techniques such as locomotor tracking, local field potential recordings and whole brain monitoring as well as a variety of molecular biology techniques. Using relevant zebrafish models, we can identify novel pharmacologically-relevant non-toxic neuroactive compounds that can be further tested in epilepsy rodent models. Additionally, if a target is known, we can validate it by generating a zebrafish CRISPR/Cas9 knockout.
Our drug discovery platform is available to industry and academia via contract research and collaborations.