Changing of the guard: transitioning from surgery to gene therapy in epilepsy treatment
Preclinical investigations demonstrate the possibility of treating epilepsy with gene therapy in mouse models of focal cortical dysplasia.
Researchers from the University College London Queen Square Institute of Neurology (UK) have demonstrated the success of gene therapy in mitigating epilepsy in mouse models of focal cortical dysplasia in the frontal lobe. These findings provide a groundwork for using gene therapy in human clinical trials for children with this condition.
Focal cortical dysplasia is a congenital condition whereby there is abnormal neural organization. It manifests in a spectrum of cognitive and behavioral abnormalities, which can co-present with severe and pharmacoresistant epilepsy. The standard treatment for this childhood epilepsy is to surgically remove the brain malformation; however, this is not guaranteed to alleviate epilepsy or prevent permanent neurological deficit.
Researchers sought to find an alternative to surgery and its associated complications. Gene therapy has already worked against other forms of epilepsy that arise in the temporal lobe and focal neocortex, so the researchers applied this methodology to epilepsy caused by focal cortical dysplasia in the frontal lobe.
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They investigated a seizure-alleviating gene therapy, which works by regulating neuronal excitability through the overexpression of potassium channels, in mouse models of the condition.
The mice’s brain activity was monitored for 15 days, after which the mice were injected with either the gene therapy or a control virus. The mice were then monitored for a further 15 days. The gene therapy supplied EKC genes, which encode engineered voltage-gated potassium channels, to principal neurons of frontal lobe tissue via adeno-associated viral vectors.
The gene therapy reduced seizures by 87% when compared to the control group, without affecting mouse memory or behavior. Encouraged by these findings, the team is planning human clinical trials to be underway in the next 5 years.
Lead author Vincent Magloire added, “following the successful study in mice, we believe the treatment is suitable for clinical translation, and, taking into account the size of the unmet need, it could be deployed to thousands of children who are currently severely affected by uncontrolled seizures.”