Gene therapy dampens epileptic seizures in early tests

Written by Alexander Marshall

Gene therapy may preemptively stop seizures in epileptics by establishing a ‘release-on-demand’ treatment in neurons

Researchers have recently developed a new gene therapy technique stemming epileptic seizures at their source. The collaboration between Charité – Universitätsmedizin Berlin (Germany) and the Medical University of Innsbruck (Austria) has demonstrated promising outcomes in animal models and human tissues, utilizing a virus to target specific regions of the brain and dampen the activity which would lead to seizures before they can begin. Current treatments for epilepsy are fraught with side effects and complications while not always being sufficiently successful at managing the condition, so researchers hope this new technique will eventually be able to aide the five million people affected across Europe.

The research, led by Regine Heilbronn (Charité- Universitätsmedizin Berlin), uses an adeno-associated virus vector to transfer a dynorphin synthesis gene into the overly active neuronal cells involved in temporal lobe epilepsy. Dynorphin is a naturally occurring peptide which can then accumulate within the cells until the neurons become overstimulated at the start of a seizure. At the start of a seizure, the dynorphins are then released and allow a dampening affect upon signal transduction. This method has been termed ‘release-on-demand’ due to the transient dynorphin wave which is released just prior to a seizure. The virus appeared capable of suppressing seizures for several months in animal models and even demonstrated the ability to reduce neuronal activity in epileptic tissue.

         We are currently working on the viral vector which ferries the gene to its destination, in order to optimize it for use in humans. Our aim is to have this gene therapy ready for its first ever use in a clinical trial in just a few years,” explained Regine.

Recurrent long-term epilepsy can have a severe impact on memory, learning and emotional control, and while drugs do exist, drug-resistant temporal lobe epilepsy is a significant issue. This often leaves surgical removal of the region as the only course of action available. Despite this, surgical treatment does not guarantee protection from seizures and can have severe cognitive implications. It is the researchers’ hope that this ‘release-on-demand’ therapy will become an effective way of treating those who are unable to manage their condition through drugs, instead utilizing a single dose of virus.

Sources: Agostinho A, Mietzsch M, Zangrandi L et al. Dynorphinbased “release on demand” gene therapy for drugresistant temporal lobe epilepsy. EMBO Mol. Med. 11(10):e9963 (2019);