Focused Ultrasound Therapy
Focused ultrasound is an early-stage, noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with Alzheimer’s disease. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects without incisions or radiation. One mechanism is the temporary opening of the blood-brain barrier (BBB), which may aid in the removal of beta amyloid or tao from the brain. In addition, potentially promising drug and antibody therapies are often limited by their inability to cross the BBB in high enough concentrations to have an impact in the brain, and opening the BBB may enable these therapeutic agents to access the brain. An additional mechanism is the ability to use neuromodulation to increase the activity of selected targets in patients with Alzheimer’s disease.
Promising preclinical studies have demonstrated the potential of focused ultrasound to enhance the delivery of therapeutic drugs or antibodies to the brain. Focused ultrasound in combination with microbubbles can safely open the BBB and enable enhanced delivery of anti-amyloid antibodies to the brain. Studies suggest that this method can reduce the number of plaques and improve cognition in Alzheimer’s disease models. Furthermore, focused ultrasound and microbubbles alone (no antibodies) have had similar effects in two different Alzheimer’s models.
- Focused ultrasound is noninvasive – no incisions, holes in the skull, electrodes in the brain – and therefore has reduced risk for infection and blood clots.
- Precise targeting minimizes damage to non-targeted healthy brain.
- Treatment can be a complement to drug therapy, enabling enhanced delivery of disease-modifying therapies into the brain via temporary opening of the blood-brain barrier.
A Phase II trial at Sunnybrook Health Sciences Centre in Toronto, Canada, is investigating the use of focused ultrasound to temporarily open the BBB in multiple regions of the brain.
A clinical trial in the US is opening the BBB with MR-guided focused ultrasound in patients with Alzheimer’s disease.
Another clinical trial in the US is opening the BBB with a neuronavigation device in patients with Alzheimer’s disease.
A clinical trial in the US is using low-intensity focused ultrasound pulsation (LIFUP) to treat patients with early Alzheimer’s disease.
An additional clinical trial in the US are treating patients with neurodegenerative dementia in Los Angeles, California. These studies are only recruiting patients by invitation.
Preclinical Laboratory Studies
Preclinical studies suggest focused ultrasound’s potential to reduce amyloid plaques and improve cognition in Alzheimer’s models. Active studies are assessing focused ultrasound-induced BBB opening to improve the delivery of:
- Anti-amyloid antibodies and other disease modifying drugs (Sunnybrook Health Sciences Centre; Columbia University; Queensland University – Australia; Brigham and Women’s Hospital)
- Anti-tau antibodies (Queensland University – Australia).
Suggested Reading: Focused Ultrasound for Alzheimer's Disease. March 2019.
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Dubey S, Heinen S, Krantic S, McLaurin J, Branch DR, Hynynen K, Aubert I. Clinically approved IVIg delivered to the hippocampus with focused ultrasound promotes neurogenesis in a model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32691-32700. doi: 10.1073/pnas.1908658117. Epub 2020 Dec 7.
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