Alzheimer's Disease

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Focused Ultrasound Therapy

Focused ultrasound is an early-stage, non-invasive, 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. Where the beams converge, the ultrasound produces a variety of therapeutic effects without incisions or radiation.

Currently, there is no cure for Alzheimer’s and few disease modifying therapies. Potentially promising drug and antibody therapies are often limited by their inability to efficiently cross the blood-brain barrier, a naturally occurring barrier of cells that inhibits the diffusion of drugs or toxins into the central nervous system.

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. Based on this preclinical evidence, a clinical trial has been organized and is underway.

Advantages:

  • Focused ultrasound is non-invasive – 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.

Clinical Trials

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A clinical trial that repeatedly opens the BBB in Alzheimer’s patients is underway at Sunnybrook Health Sciences Centre in Toronto, Canada. The trial aims to use focused ultrasound and microbubbles to temporarily open the BBB in patients with mild to moderate AD. This early-stage study will assess the safety, feasibility and reversibility of BBB opening as well as the reproducibility of repeated BBB opening in human patients.

Read the announcement about this study.

This study is only open to Canadian residents. For more information, please contact Alison Bethune at or 416-480-6100 ext.3773.

See here for a list of treatment sites
See here for a list of clinical trials sites
See here for a list of laboratory research sites

Pre-clinical Laboratory Studies

Pre-clinical 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).

Additional Information

Alzheimer’s Association
ExAblate Neuro by Insightec LTD

Notable Papers

Focused ultrasound as a novel strategy for Alzheimer's disease therapeutics. Meng Y, Volpini M, Black S, Lozano AM, Hynynen K, Lipsman N. Ann Neurol. 2017 Apr 10. doi: 10.1002/ana.24933. [Epub ahead of print]

Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model. Nisbet RM, Van der Jeugd A, Leinenga G, Evans HT, Janowicz PW, Götz J. Brain. 2017 Mar 4. doi: 10.1093/brain/awx052. [Epub ahead of print]

Burgess A, Hynynen K. Microbubble-Assisted Ultrasound for Drug Delivery in the Brain and Central Nervous System. Adv Exp Med Biol. 2016;880:293-308. doi: 10.1007/978-3-319-22536-4_16.

Focused Ultrasound for Alzheimer's Workshop SummaryFocused Ultrasound for Alzheimer's Workshop Summary - September 2015

Meairs S. Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles. Pharmaceutics. 2015 Aug 31;7(3):275-93. doi: 10.3390/pharmaceutics7030275.

Leinenga G and Götz J. Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. Sci. Transl. Med. 2015;7:278ra33.

Burgess A, Dubey S, Yeung S, Hough O, Eterman N, Aubert I, Hynynen K. Alzheimer Disease in a Mouse Model: MR Imaging-guided Focused Ultrasound Targeted to the Hippocampus Opens the Blood-Brain Barrier and Improves Pathologic Abnormalities and Behavior. Radiology. 2014 Dec;273(3):736-45.

Click here for additional references from PubMed.

     

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