Focused Ultrasound Reduces Alzheimer’s Pathology

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Key Points

  • A team at Columbia University published preclinical and clinical data suggesting focused ultrasound blood-brain barrier opening reduced two types of pathology in Alzheimer’s brains.
  • Preliminary results from the human clinical trial showed a temporary decrease of amyloid in the treated area.
Source: Karakatsani ME, Ji R, Murillo MF, Kugelman T, Kwon N, Lao YH, Liu K, Pouliopoulos AN, Honig LS, Duff KE, Konofagou EE. Focused ultrasound mitigates pathology and improves spatial memory in Alzheimer's mice and patients. Theranostics 2023; 13(12):4102-4120. doi:10.7150/thno.79898. https://www.thno.org/v13p4102.htm
Source: Karakatsani ME, Ji R, Murillo MF, Kugelman T, Kwon N, Lao YH, Liu K, Pouliopoulos AN, Honig LS, Duff KE, Konofagou EE. Focused ultrasound mitigates pathology and improves spatial memory in Alzheimer’s mice and patients. Theranostics 2023; 13(12):4102-4120. doi:10.7150/thno.79898. https://www.thno.org/v13p4102.htm

Focused Ultrasound Mitigates Pathology and Improves Spatial Memory in Alzheimer’s Mice and Patients

A collaborative research team of engineers and clinicians led by Elisa Konofagou, PhD, at Columbia University recently published results from their preclinical and clinical studies to determine whether opening the blood-brain barrier (BBB) with focused ultrasound can reduce brain plaques found in Alzheimer’s disease.

Although previous studies have shown that focused ultrasound can reduce either amyloid plaques or tau proteins, the group was the first to use a preclinical model containing both pathologies and translate the work to a human clinical trial (data presented from one participant). Both pathologies are present in people who have Alzheimer’s disease.

The objective of the study was to investigate whether repeated (weekly), bilateral focused ultrasound BBB sonication could reduce the volume of plaques and proteins in brains with both pathologies and improve memory. The treatment did both, and cognitive improvement correlated with the volume of BBB opening (with statistically significant measurements).

The human clinical trial (NCT04118764) used Columbia’s neuronavigation-guided focused ultrasound system. Preliminary results from the positron emission tomography (PET) scan done three weeks after treatment showed a 1.8% decrease from baseline of amyloid in the treated area. This reduction in amyloid was statistically significant but short-lasting. The amyloid reduction ended up being temporary, with PET amyloid signals increasing over time. Therefore, the researchers suggested that repeated treatments might produce a therapy option for patients living with this devastating disease.

Additional future steps include optimizing the treatment regimen (i.e., brain target, opening frequency, opening volume), covering a larger region of the brain across multiple sessions, and delivering therapeutics (e.g., small molecules, neurotrophic factors, antibodies).

The study was funded by several grants from the National Institutes of Aging and the National Center for Advancing Translational Sciences of the National Institutes of Health, and the support of the Focused Ultrasound Foundation.

See Theranostics

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