Abstract
The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.
Highlights
The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders
High-intensity focused ultrasound (FUS) is used for treatment of tremor, while low-intensity FUS is being explored for BBB opening [4, 5]
We report early safety and feasibility outcomes in Alzheimer’s disease (AD) patients from a multicenter FUS treatment study targeting a substantial portion of the deep and complex structures of the hippocampus and entorhinal cortex (EC)
Summary
The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions. Animal studies have demonstrated safe and reversible BBB opening [4, 6, 7] as well as reduction of amyloidbeta plaque, neurogenesis, and improvement of memory This technology enables targeted noninvasive delivery of genetic vectors and cells [6, 8,9,10]. We report early safety and feasibility outcomes in AD patients from a multicenter FUS treatment study targeting a substantial portion of the deep and complex structures of the hippocampus and entorhinal cortex (EC)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
