Background
- Current antiseizure medicines primarily control symptoms rather than prevent epilepsy development or progression, and nearly one-third of people with epilepsy remain drug resistant.
- Oxidative stress contributes to epileptogenesis, but sustained antioxidant activation can disrupt normal redox signaling, highlighting the need for targeted, responsive treatment.
Our Innovation
- An activity-responsive AAV9 gene therapy links expression of Nrf2, a regulator of antioxidant defenses, to the neuronal cfos promoter, which is activated by pathological neuronal hyperactivity.
- The system transiently activates antioxidant pathways in predominantly excitatory neurons in affected hippocampal circuits, rather than driving continuous expression.
- The approach has been evaluated following targeted hippocampal delivery in rodent models of epilepsy, both before and after chronic seizures were established.
Advantages
- On-demand, activity-dependent engagement of antioxidant defenses, with limited baseline expression in the tested models.
- Reduced spontaneous seizure frequency and cumulative seizure burden, with more seizure-free days, during 12 weeks of monitoring in a preclinical model of epilepsy development.
- Reduced cumulative seizure burden when administered after chronic epilepsy was established, although seizures were not eliminated.
- Improved performance in preclinical assessments of working memory, locomotion and anxiety-like behavior compared with control animals.
Commercial Opportunity
A preclinical gene-therapy opportunity for drug-resistant focal epilepsy and potential early intervention during epileptogenesis. We welcome partners in neurology and gene therapy to advance delivery, safety, biodistribution and clinical translation.
Learn more: https://doi.org/10.1038/s41392-026-02738-w
