Neurologist receives ERC grant to study novel light-activated drugs with antiepileptic effects

Dr. Michael Wenzel from the Department of Epileptology at the University Hospital Bonn has received a coveted Starting Grant from the European Research Council (ERC). With the associated funding of 1.5 million euros for the next five years, the neurologist wants to study novel light-activated drugs with antiepileptic effects investigating how they can help against hard-to-treat epilepsies.

The ERC Starting Grant is aimed at excellent young scientists at the beginning of an independent career. Dr. Michael Wenzel is working on epilepsy - a neurological disease affecting more than 50 million people worldwide. "Despite a steadily increasing number of antiepileptic drugs, around 30 percent of epilepsies cannot be controlled with medication," says Wenzel. If antiepileptic drugs are used, they often have side effects, for example on the heart, the ability to think, the psyche or the unborn child during pregnancy. Alternatively, there are surgical measures, but these are only an option for a fraction of those affected.

An efficient antiepileptic therapy with few side effects would therefore be of enormous value for patients with hard-to-treat epilepsy."

Dr. Michael Wenzel, Department of Epileptology, University Hospital Bonn

This is precisely what the newly funded project aims to establish. Michael Wenzel and his team target so-called photo-activatable agents. The special feature about this type of drugs is that they only develop their effect when they are irradiated with light. This allows doctors to "switch them on" at exactly the place in the body where they are needed. In the project, the researchers use substances with high antiepileptic efficacy from other disciplines, such as the substance propofol from anesthesiology. The goal is to chemically modify the substances so that they only become active in a specific brain region when exposed to light of a certain wavelength. "Local light activatability allows us to adopt effective substances with different targets from other disciplines for epileptology and minimize drug side effects on the body," says Michael Wenzel.

How does the method work?

What is needed is a biocompatible light source that targets a specific brain region, for example via depth electrodes. The goal of the ERC project is to first test in mice whether the approach works at all. To this end, Wenzel and his team use state-of-the-art optical and electrophysiological in vivo methods. In addition, the drugs will be tested in acute brain slices of surgically removed brain tissue from patients with hard-to-treat epilepsy.
Another highlight of the project: "We are not only testing light-activatable drugs that can suppress epileptic seizures, but also those that could change the course of the disease," says Wenzel. This could work, for example, by interfering with disease-promoting inflammatory processes. In this way, the project goes beyond the symptomatic therapy of epilepsy.

"The basic idea of the project's approach is similar to other light-based therapeutic approaches, for example optogenetics. However, in our case, no viral transfer is needed to deliver the light-activatable agent to the site of action," explains Michael Wenzel. Instead, the drug is supposed to reach the brain via the circulatory system. Another main advantage is that the therapeutic regimen could be flexibly changed using different light-activatable drugs with the same light source.

Interdisciplinary teamwork

For the project, Michael Wenzel brings together a variety of disciplines under one roof spanning epileptology, basic neurobiology and medicinal chemistry. "Even though I lead the project as a clinician scientist bridging and linking all project levels, the design and synthesis of the investigated substances is of course done in a joint effort with others, first and foremost Prof. Christa Müller here in Bonn," says Michael Wenzel who is also a member of the Transdisciplinary Research Area "Life and Health" at the University of Bonn. "A single person could hardly cover all expertise needed to realize a research project like this", he emphasizes.

About the person

Michael Wenzel, born in 1982, studied human medicine and received his doctorate from Ludwig Maximilian University Munich. He also started his clinical training in neurology there until 2013. In 2014, he started a postdoctoral position at Columbia University in New York focusing on cellular mechanisms of epileptic micronetworks. Since 2019, he leads a junior research group at the Department of Epileptology in Bonn, in cooperation with the Institute for Experimental Epileptology and Cognition Research. He is a Clinician Scientist in the Hertie Network of Excellence in Clinical Neuroscience and works as a physician at the Department of Epileptology at the University Hospital Bonn.