Scientists Innovate Seizure Control with Sound Waves and Gene Therapy

Scientists at Rice University have developed a groundbreaking method to control seizure-related brain activity using a combination of sound waves and gene therapy. This innovative approach, which has demonstrated success in animal models, offers a targeted, nonsurgical solution for epilepsy by focusing on the hippocampus, a brain region commonly associated with seizures.

The research team, led by assistant professor of bioengineering Jerzy Szablowski, utilized low-intensity focused ultrasound to temporarily open the blood-brain barrier, allowing for precise intervention without invasive procedures. “Many neurological diseases are driven by hyperactive cells at a particular location in the brain,” Szablowski stated. “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.”

Innovative Method Combines Ultrasound and Gene Therapy

The technique, known as acoustically targeted chemogenetics (ATAC), combines ultrasound with gene therapy and chemogenetics to selectively activate or deactivate neurons using a targeted drug. In this process, tiny, gas-filled bubbles are injected into the bloodstream. When ultrasound waves are directed at the hippocampus, these bubbles expand and create temporary openings in the blood-brain barrier. These openings are large enough for gene therapy vectors to enter the targeted tissue but small enough to close naturally within hours.

The engineered vectors carry genetic instructions for an inhibitory chemogenetic receptor, acting like a molecular “dimmer switch” that enables neurons to respond to a drug designed to quell overactivity. According to Honghao Li, a doctoral student in bioengineering and the study’s first author, “By precisely targeting the hippocampus, we can dampen overactivity where it matters and leave the rest of the brain untouched.”

The findings indicate that the ATAC method can effectively modulate specific brain circuits through a minimally invasive procedure and a straightforward drug application. Since both focused ultrasound and viral vector gene delivery are already under investigation in clinical trials, the researchers believe this could accelerate the development of new treatments for epilepsy and other neurological disorders.

A Flexible Platform for Neurological Treatments

This study represents a significant milestone for Szablowski’s team, which has previously demonstrated methods for delivering gene therapies across both large and small brain regions. The lab has also created another ultrasound-based technique called recovery of markers through insonation (REMIS). This method facilitates the release of proteins from specific brain areas into the bloodstream for monitoring purposes.

“Ultrasound lets us deliver therapy, control the neurons we want and then measure the effects in the exact circuit we targeted,” Szablowski explained. The overarching goal is to establish a flexible platform capable of safely reaching any brain region, delivering genetic material with precision, and allowing clinicians to control the therapy on demand.

This research underscores Rice University’s expanding focus on brain science and neurological health, now integrated under the new Rice Brain Institute. The findings of this study are documented in the journal ACS Chemical Neuroscience, marking a pivotal step forward in non-invasive neurological treatments and the future of epilepsy management.