Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model

We congratulate the authors for this important work demonstrating that focused ultrasound (FUS) combined with microbubbles and applied in a scanning method across the entire brain reduced the number and volume of amyloid plaques and improved memory in the APP23 mouse model of Alzheimer's disease (AD).

This work corroborates studies from Kullervo Hynynen, Isabelle Aubert, and colleagues at Sunnybrook Health Sciences Centre in Toronto, who first published data suggesting the benefit of FUS and microbubbles to open the blood brain barrier (BBB) and reduce plaque burden and improve memory-based behavior in a different AD model, the TgCRND8 mouse. They applied the ultrasound in discrete regions of the brain rather than to the entire brain, as done by Leinenga and Gotz. As the mechanisms of this approach are explored further and the therapeutic potential optimized, it is important to consider the broader history of FUS studies in the CNS.

To date, more than 300 patients with various neurological disorders including essential tremor and Parkinson's disease have been treated with non-invasive magnetic resonance guided FUS via thermal ablation of precise targets deep in the brain. Robust preclinical work is ongoing at several global sites using FUS plus microbubbles to open the BBB and deliver large molecules including drugs, DNA-loaded nanoparticles, viral vectors, and antibodies, in models of AD, Parkinson's disease and glioma.

With the paper by Leinenga and Gotz, there is now evidence from two separate laboratories using two different AD mouse models to demonstrate that FUS and microbubbles alone can open the BBB and reduce plaque burden, with no unwanted damage to brain tissue. While preliminary, having two validated approaches is very promising. Following up these data with a successful safety and feasibility study for opening the BBB in humans, which is beginning soon at Sunnybrook in Toronto could provide the essential predicate for an AD clinical trial.

In addition, safe, reliable and temporary opening of the BBB remains an unmet critical medical need for treatment of a range of diseases. Furthermore, the ability of FUS to non-invasively induce various other effects in the brain - precise ablation, immunomodulation, neuromodulation - offers potential future benefits to disorders beyond Alzheimer's, including Parkinson's, epilepsy, and glioblastoma, with the potential to impact countless patients worldwide. The Focused Ultrasound Foundation, a 501(c)(3) organization, is advancing this field through alignment of efforts and collaboration across disciplines to bring this promising therapy to patients as quickly as possible.