MaxWell Webinar with Dr. Marcus Kaji

Due to confidentiality reasons, this webinar was not recorded. Stay tuned for future webinars, and make sure not to miss them!

This webinar will covered:

The role of KCNQ2 in neurodevelopment, including the outcomes of this gene mutation

Unique network characteristics identified for both KCNQ2 loss- and gain-of-function

How these findings can support drug development efforts for KCNQ2 disorders

HD-MEA’s contribution to expanding the toolkit for screening new therapies with human-derived in vitro models

Speaker

Dr. Marcus Kaji
Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology
Belgium

Host

Dr. Laura D’Ignazio
MaxWell Biosystems
Switzerland

Title

Modeling KCNQ2 Epilepsy in iPSC Neurons for Targeted Drug Testing

Abstract

The study of dysfunctional human neuronal network development is a challenging topic, made more approachable with advances in the combination of human iPSC neurons and HD-MEA technology. This cutting edge combination allows our lab to investigate the neurodevelopmental role of KCNQ2, a gene encoding a potassium channel crucial for regulating the resting membrane potential and modulating neuronal excitability. Pathogenic variants in KCNQ2 cause a range of developmental and epileptic encephalopathies, often featuring seizures and lifelong intellectual disability with no treatment options available apart from general antiseizure medication.
In this webinar, I will present findings from two-month longitudinal recordings of networks harboring loss-of-function (LOF) and gain-of-function (GOF) and KCNQ2 variants, highlighting distinct network characteristics associated with each. Leveraging these dysfunctional network phenotypes, I will showcase how this model supports novel drug screening efforts highlighted by A) acute treatment with channel modulators in a KCNQ2-LOF background and B)chronic treatment with a novel antisense oligonucleotide targeting gene expression knockdown in KCNQ2-GOF networks. Insights gained from these HD-MEA recordings, particularly chronic drug testing in a human in vitro model, represents an important expansion of our toolkit for screening novel treatments of monogenic neurodevelopmental disorders.

Speaker Bio

Marcus Kaji is a postdoctoral fellow at the VIB -University of Antwerp Center for Molecular Neurology in the laboratory of Prof. Sarah Weckhuysen. Marcus holds a PhD in Molecuar Parasitology from McGill University where he studied the druggability of ligand-gated ion channels from parasitic nematodes. Since joining the Weckhuysen lab in 2021, Marcus recieved an FWO fellowship to study developmental and epileptic encephalopathies caused by pathogenic variants in voltage-sensing potassium channels. His research primarily focuses on using HD-MEAs to characterize mutant neuronal networks and search for novel drug targeting strategies.