Focal epilepsies are often difficult to treat with medication. A new gene therapy being developed by a Charité spin-off gives hope. The approach has already been successful in animal experiments. Clinical studies are now to follow.
Recurrent epileptic seizures are extremely distressing. In order to prevent renewed “lightning storms in the head”, the patients have to take medication permanently. However, in focal epilepsies, where the seizure origin is concentrated in a specific area of the brain, drugs often fail and have severe side effects. Some patients may also undergo surgery. But even epilepsy surgery does not guarantee permanent freedom from seizures.
“Unfortunately, we can’t really help many of those affected,” says Prof. Regine Heilbronn, from the Charité Clinic for Neurology and co-founder of EpiBlok GmbH, a spin-off of the Charité and the Medical University of Innsbruck. “That’s why we have developed a conceptually new therapeutic approach.”
Missing neuropeptide is replaced
The new approach is based on the knowledge that the concentration of the neuropeptide dynorphin is often too low in focal epilepsy. The small protein ensures that groups of nerve cells cannot simultaneously discharge in an uncontrolled manner, as is the case with an epileptic seizure. In gene therapy, the scientists introduce the dynorphin gene into the affected nerve cells using a gene vector. The vehicles for the dynorphin gene are adeno-associated virus vectors (AAV), which have already been clinically approved for gene therapy of some diseases.
In mice, the researchers were able to show that the animals produce and store the dynorphin peptide after treatment. After a single application, the epileptic seizures were reliably suppressed for several months, the researchers report.
„Drug on demand“-Therapie
“In this case it is a “drug on demand” therapy: The nerve cells only release the stored peptide when it is needed,” explains Prof. Christoph Schwarzer, neuropharmacologist at the University of Innsbruck, and co-founder of EpiBlok. “This is the case when the nerve cells are constantly excited, as at the beginning of an epileptic seizure. The dynorphin then inhibits the excitement and the thunderstorm subsides.”
Clinical study in preparation
The team led by Regine Heilbronn and Christoph Schwarzer is now planning the first clinical study. “With EpiBlok Therapeutics GmbH, we want to produce the AAV vector in larger quantities and in the required high quality in order to initiate an initial clinical study,” says Heilbronn.
When founding EpiBlok GmbH, Regine Heilbronn’s team was supported by the SPARK BIH program with funding, coaching and mentoring. For the preclinical studies on the AAV-based gene therapy against focal epilepsy, Regine Heilbronn has already received funding of 3.3 million euros from the GO Bio program of the Federal Ministry of Research. According to the Charité, EpiBlok is their first spin-off to pursue a gene therapy treatment approach.