The preclinical project will utilize Precise Intracerebral Noninvasive Guided surgery – or PING – in an animal model of temporal lobe epilepsy. Low-intensity focused ultrasound will be used to open the blood-brain barrier (BBB) and deliver a systemically administered neurotoxin to the brain parenchyma in a targeted area that is responsible for generating seizures. The brain parenchyma typically has low permeability to most drugs, but studies indicate that focused ultrasound can temporarily loosen the BBB’s tight cell structure, and thus noninvasively allow the toxin to enter the desired portion of the brain. Researchers believe the toxin will destroy the seizure-generating neurons without harming the nerve axons or vasculature that are passing through the same area.
“The goal of this study is to create axon-sparing lesions in order to reduce or eliminate seizures,” explains Dr. Lee. “High-intensity focused ultrasound has proven to be a good tool for creating ablation lesions in the midline structures of the brain. If we’re successful, this study will hopefully enable researchers to expand focused ultrasound’s treatment envelope to locations that were previously off the table. And, it could allow greater cellular specificity, potentially sparing non-target axonal and vascular elements.”
Dr. Lee’s team’s research will take place in tandem with a separate clinical trial at UVA assessing the feasibility, safety and initial effectiveness of focused ultrasound to ablate diseased brain tissue in patients with epilepsy. That trial is being led by Nathan Fountain, MD, Professor of Neurology at UVA.
Dr. Lee’s project was initially selected as part of the Foundation’s external awards program last year. However, with the award of this grant, Lee plans to return the Foundation’s funding in hopes that it will support other important projects.
“I’m appreciative of the Foundation’s efforts in accelerating the field of focused ultrasound,” shares Dr. Lee. “I attended the Blood-Brain Barrier Workshop in November, which was an opportunity to interact with other researchers in the field and discuss ideas that can really push the envelope of what we currently believe is possible. My hope is that our team’s research will contribute to this goal.”
NINDS was created in 1960 with the mission to “reduce the burden of neurological disease—a burden borne by every age group, every segment of society, and people all over the world.” To do so, they support thousands of research projects at institutions across the country as well as conduct their own research in the major areas of neuroscience and train investigators.