Groundbreaking Ultrasound Technique Offers Non-Surgical Hope for Neurological Disorders
A new, minimally invasive procedure utilizing focused ultrasound adn gene therapy has demonstrated the ability to precisely modulate brain activity in an animal model, offering a potential breakthrough in the treatment of epilepsy and other neurological conditions. Researchers at Rice university have developed a method to temporarily open the blood-brain barrier (BBB), deliver targeted gene therapy, and then control the therapeutic effect on demand with an oral drug – all without the need for surgery or permanent implants.
The research, published in ACS Chemical Neuroscience, builds upon nearly a decade of work refining a technique called acoustically targeted chemogenetics (ATAC). This innovative approach combines the precision of ultrasound, the potential of gene therapy, and the control of chemogenetics – a method of equipping neurons with engineered receptors responsive to specific drugs – into a single, powerful tool.
In the ATAC procedure,microscopic gas-filled bubbles are first injected into the bloodstream. Low-intensity ultrasound waves are then directed at the hippocampus, a brain region frequently enough implicated in seizures and other neurological disorders.These waves cause the microbubbles to gently oscillate against blood vessel walls, creating temporary, nanometer-scale openings in the BBB. These openings, while large enough to allow the passage of engineered gene delivery vectors, are significantly smaller than blood cells, preventing their entry. The BBB naturally reseals within hours.
These engineered vectors carry the genetic instructions for building an inhibitory chemogenetic receptor, effectively a molecular “dimmer switch” that allows researchers to quiet overactive neurons with a subsequent dose of oral medication. “By precisely targeting the hippocampus, we can dampen overactivity where it matters and leave the rest of the brain untouched,” explained Honghao Li, a bioengineering doctoral student at Rice and a first author on the study.
The teamS approach offers a notable advantage over existing treatments for neurological disorders, many of which involve systemic medication with widespread effects or invasive surgical procedures. “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 University neuroengineering Initiative. “Our approach aims the therapy where it is indeed needed and lets you control it when you need it, without surgery and without a permanent implant.”
This isn’t the first time Szablowski’s team has demonstrated the power of targeted gene delivery. They have previously shown success in delivering therapies across varying brain volumes, from large areas to individual neuronal connections. Moreover, the researchers have developed a complementary technique called recovery of markers through insonation (REMIS), which uses focused ultrasound to release engineered or natural proteins from targeted brain regions into the bloodstream, allowing for non-invasive monitoring of gene activity. Reader question: How does REMIS contribute to the overall effectiveness of the ATAC method? This REMIS technique is already being explored in a clinical trial with partners at baylor College of Medicine and the University of Texas MD Anderson Cancer Center.
The potential implications of this research extend beyond epilepsy. As both focused ultrasound BBB opening and viral vector-based gene delivery are already being investigated in clinical trials, the ATAC method could accelerate the development of targeted therapies for a wide range of neurological disorders, including Parkinson’s disease and other conditions characterized by localized brain hyperactivity. “Ultrasound lets us deliver therapy, control the neurons we want and then measure the effects in the exact circuit we targeted,” Szablowski stated.”Our goal is to build a platform that can reach any brain region safely, deliver any genetic payload precisely and let clinicians control it on demand. This kind of versatility could change how we think about developing brain therapies.”
The research was supported by the G. Harold & Leila Y. Mathers Foundation, michael J. Fox Foundation for parkinson’s Disease Research, the National Institutes of Health, and the National Science Foundation. The authors emphasize that the content of this press release is their sole responsibility and does not necessarily reflect the official views of the funding organizations and institutions.
