Scientists Pioneer Non-Surgical Method for Seizure Control

Researchers at Rice University have unveiled a groundbreaking approach to managing epilepsy through a novel combination of sound waves and gene therapy. This innovative technique demonstrates a targeted, non-surgical method capable of effectively regulating brain activity associated with seizures.

The study, published in the journal ACS Chemical Neuroscience, showcases how bioengineers can utilize low-intensity focused ultrasound to temporarily open the blood-brain barrier. This allows for the precise delivery of gene therapy specifically to the hippocampus, a brain region often implicated in seizure disorders. The results indicate that a single, carefully directed procedure can modulate problematic brain circuits without impacting surrounding areas.

Led by Jerzy Szablowski, an assistant professor of bioengineering, the research team has developed a method known as acoustically targeted chemogenetics, or ATAC. This technique integrates ultrasound with gene therapy and chemogenetics, enabling targeted activation or deactivation of specific neurons through an oral drug. Szablowski noted, “Many neurological diseases are driven by hyperactive cells at a particular location in the brain. 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 process begins with the injection of tiny, gas-filled bubbles into the bloodstream. When ultrasound waves focus on the hippocampus, these bubbles impact the walls of blood vessels, creating temporary, microscopic openings in the blood-brain barrier. These openings allow gene therapy vectors to enter the targeted tissue, while naturally closing within hours.

The engineered vectors carry genetic instructions for an inhibitory chemogenetic receptor, acting as a molecular “dimmer switch.” This mechanism allows researchers to modulate neuronal activity precisely. Lead author Honghao Li, a bioengineering doctoral student, explained, “By precisely targeting the hippocampus, we can dampen overactivity where it matters and leave the rest of the brain untouched.”

The findings from this research suggest that the ATAC approach could significantly accelerate the development of new treatments for epilepsy and potentially other neurological disorders. Both focused ultrasound and viral vector gene delivery are currently under investigation in clinical trials, indicating a promising future for these technologies.

This study represents a significant advancement for Szablowski’s team, which has also explored various methods for delivering gene therapies across different brain regions. Their ultrasound-based technique, known as recovery of markers through insonation (REMIS), allows for the release of proteins from specific brain areas into the bloodstream for monitoring purposes.

“These technologies complement each other,” Szablowski added. “Ultrasound lets us deliver therapy, control the neurons we want, and then measure the effects in the exact circuit we targeted.”

The ultimate objective is to create a flexible platform that can safely reach any brain region, delivering genetic material accurately and allowing clinicians to exert control on demand.

This research underscores Rice University’s commitment to advancing brain science and neurological health, now unified under the newly established Rice Brain Institute. The innovative work paves the way for future breakthroughs in the treatment of epilepsy and other neurological conditions, offering hope for patients seeking effective, non-invasive therapies.