Skip to main content

A novel gene therapy for epilepsy

Article Category

Article available in the folowing languages:

Gene therapy for epilepsy: moving beyond current state-of-the-art treatment

Epilepsy is a recurrent neurological disorder, and many cases demonstrate drug resistance. A novel treatment strategy based on seizure-modulating genes brings hope for a positive clinical outcome in patients.

Industrial Technologies

Epilepsy is associated with increased excitability in the brain, which leads to recurrent, unprovoked seizures, most often of unknown aetiology. Disease presentation is highly variable, and conventional treatment entails the use of anti-epileptic drugs that help reduce the severity and frequency of seizures. However, current pharmacologic approaches lead to unsatisfactory therapeutic efficacy for a significant number of individuals who may develop resistance to available drugs, necessitating the development of novel therapies.

Gene delivery to contain epileptic seizures

Accumulating evidence suggests that gene therapy may be an attractive approach for limiting seizures. The heterogeneity among individuals and the inability to identify disease-causing mutations has stirred efforts towards the regulation of inhibitory peptides implicated in brain hyperexcitability. The EU-funded CG01 project has developed a strategy that delivers the human neuropeptide Y (NPY) and the neuropeptide Y2 receptor as a means of inhibiting seizures. “Our strategy employs adeno-associated virus (AAV) vectors, a safe and efficient gene transfer approach for the nervous system,” explains Jan Nilsson, project coordinator and chief executive officer at CombiGene. Although AAV is not known to cause disease, it is essentially stripped off its viral elements and only serves as a vehicle for gene transport into cells. The rationale behind the expression of NPY and its Y2 receptor is to inhibit the continuous release of glutamate neurotransmitters at neuronal synapses and minimise hyperexcitability that is responsible for seizures. The simultaneous expression of these two genes seems to have a synergistic anti-seizure effect in animal models of epilepsy as a proof of concept. The team has undertaken additional preclinical studies such as a dose response evaluation in small animals and a study in human brain tissue. Moreover, they have established a scalable production method. “The biggest achievement of the project was the ability of the team to achieve the expected milestones, without any significant delays, through a successful journey,” outlines Nilsson.

CG01 prospects in the clinic

CombiGene has entered an exclusive collaboration and licensing agreement with Spark Therapeutics in 2021 for the CG01 project. The two companies will jointly conduct the final parts of the preclinical programme with important biodistribution and toxicology studies. Once the preclinical programme is finalised, Spark Therapeutics will assume full responsibility for running the clinical programme and further developing, manufacturing and commercialising the CG01 advanced therapy medicinal product. The clinical trial will initially include patients eligible for surgery. Depending on the result, the study is expected to lead to further clinical development and evaluate the efficacy of the gene therapy solution in a larger group of patients. According to Nilsson, “the most important thing about CG01 is that it offers pharmacoresistant epilepsy patients an effective alternative that will improve the quality of their lives.” Successful completion of the CG01 project will offer people with epilepsy an effective, first in class gene therapy without the adverse side effects of the currently available medications. Moreover, the CG01 technology could be exploited for the gene therapy of other diseases.


CG01, epilepsy, gene therapy, AAV, NPY, neuropeptide Y receptor Y2, adeno-associated virus, human neuropeptide Y, drug resistance

Discover other articles in the same domain of application