The blood-brain barrier as a target for diagnosis and treatment in Epilepsy

Approximately a third of patients with epilepsy do not respond to existing medications and continue to experience seizures. Such patients may be candidates for epileptic surgery, which aims to remove the seizure onset zone (SOZ) from the brain. However, accurate identification of the SOZ remains challenging, and patients often continue to experience seizures following surgery.

This project aims to close two gaps in epilepsy care by: (1) developing a new diagnostic tool for accurate SOZ identification; and (2) test a novel treatment for epilepsy — targeting a specific molecular mechanism that underlies seizures.

In previous animal and human studies, we have shown that dysfunction of the brain’s small blood vessels — specifically a leaky blood-brain barrier (BBB) — plays a critical role in the development of epilepsy. We have also: (1) developed and validated a brain imaging method for detecting a leaky BBB in human patients and in animals (using magnetic resonance imaging — MRI); and (2) discovered a drug that can repair a leaky BBB and prevent the development of epilepsy.

Here, we aim to validate the ability of our diagnostic approach to identify the SOZ in patients with epilepsy. We will also conduct a pre-clinical trial testing the efficacy of BBB repair as a treatment for epilepsy in a rat model of the disease.

This collaborative, translational research has the potential to yield a new diagnostic test for objective and reliable localization of seizure-origins in the brain, and a novel mechanism-specific treatment to cure epilepsy.