Focal epilepsies are often difficult to treat with medication. A new gene therapy developed by a Charité spin-off gives hope. The approach has already been successful in animal experiments. Clinical trials must now follow.
Recurrent seizures are extremely painful. In order to prevent new “lightning storms to the head”, patients must take medications permanently. However, in focal epilepsies, where the source of the seizure is concentrated in a specific area of the brain, drugs often fail and have severe side effects. Some patients may even undergo surgery. But even epilepsy surgery does not guarantee permanent freedom from seizures.
“Unfortunately, we cannot really help many of those affected,” says Prof. Regine Heilbronn, of the Charité Clinic for Neurology and co-founder of EpiBlok GmbH, a spin-off of the Charité and the University of Medicine of Innsbruck. “That is why we have developed a conceptually new therapeutic approach.”
The missing neuropeptide is replaced
The new approach is based on the finding that the concentration of the neuropeptide dynorphin is often too low in focal epilepsy. The small protein ensures that groups of nerve cells cannot discharge simultaneously in an uncontrolled way, as in the case of a seizure. In gene therapy, scientists introduce the dynorphin gene into affected nerve cells using a gene vector. The vehicles of the dynorphin gene are adeno-associated virus (AAV) vectors, 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 seizures were reliably suppressed for several months, the researchers report.
“Drug on demand” therapy.
“In this case it is a” drug on demand “therapy: the nerve cells release the stored peptide only when it is needed”, explains prof. Christoph Schwarzer, neuropharmacologist at the University of Innsbruck and co-founder of EpiBlok. “This is the case where nerve cells are constantly excited, like at the start of a seizure. Dynorphin then inhibits arousal and the storm subsides.”
Clinical study in preparation
The team led by Regine Heilbronn and Christoph Schwarzer is now planning the first clinical trial. “With EpiBlok Therapeutics GmbH, we want to produce the AAV vector in larger quantities and in the high quality required to start an initial clinical trial,” says Heilbronn.
When he founded EpiBlok GmbH, Regine Heilbronn’s team was supported by the SPARK-BIH program with funding, coaching and mentoring. For preclinical studies on AAV-based gene therapy against focal epilepsy, Regine Heilbronn has already received a grant 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.