AVanti-134 (AAV9-anti-miR-134): A microRNA-based disease-modifying gene therapy for refractory epilepsy

Background: There are urgent and unmet therapeutic needs for people with drug-resistant epilepsy. We have found elevated brain levels of a molecule called microRNA-134 in human and experimental drug-resistant epilepsy and shown a synthetic drug (antisense) that inhibits microRNA-134 produces powerful and prolonged anti-seizure effects in animal models. Approach: We propose to develop a gene therapy-based treatment for drug-resistant epilepsy that uses a virus, called AAV9, to produce safe and sustained inhibition of microRNA-134 in specific brain cells. Advantages: Our gene therapy approach uses an already clinically-approved virus and will deliver sustained inhibition of the target microRNA-134 in specific brain cell types. This avoids common pitfalls of antisense-like drugs which enter all cells and require repeated and uncomfortable administration into the cerebrospinal fluid. Impact: A clinical trial-ready gene therapy with a unique mechanism of action that can reduce and prevent seizures in this devastating and common form of epilepsy.