New approach for targeted seizure control without surgery

“Many neurological diseases are driven by hyperactive cells at a particular location in the brain,” said study lead Jerzy Szablowski, assistant professor of bioengineering and a member of the Rice Neuroengineering Initiative. “Our approach aims the therapy where it is needed and lets you control it when you need it, without surgery and without a permanent implant.”

The work builds on nearly a decade of innovation by Szablowski and his team. The group’s acoustically targeted chemogenetics (ATAC) method merges ultrasound, gene therapy and chemogenetics ⎯ a technique that equips selected neurons with engineered receptors so they can be activated or silenced by a specific drug ⎯ into a single tool that makes possible precise control over brain circuits without surgery.

In the ATAC procedure, researchers first injected microscopic gas-filled bubbles into the bloodstream. When low-intensity ultrasound waves were directed at the hippocampus, the microbubbles oscillated gently against blood vessel walls, creating temporary, nanometer-scale openings in the BBB. These pores were hundreds of times smaller than blood cells ⎯ thus impeding their passage ⎯ but large enough to allow engineered gene delivery vectors developed by the Szablowski lab to enter the targeted brain tissue. The pores closed naturally within hours, leaving the BBB intact.

The engineered vectors carried instructions for building an inhibitory chemogenetic receptor ⎯ a kind of molecular “dimmer switch” that makes neurons responsive to a drug administered later to “quiet” seizure-inducing activity. “By precisely targeting the hippocampus, we can dampen overactivity where it matters and leave the rest of the brain untouched,” said Honghao Li, a bioengineering doctoral student at Rice who is a first author on the study.

The results confirm that ATAC can achieve precise control over target brain circuits using a minimally invasive procedure and a simple systemic drug. Because both focused ultrasound BBB opening and viral vector-based gene delivery are already advancing in clinical studies, the method could accelerate the development of targeted treatments for epilepsy and other neurological disorders.