Alzheimer's Disease

Background

Clinical KeyAlzheimer’s disease (AD) is a progressive neurodegenerative brain disease which attacks the neurons in the brain, leading to cell death and degeneration. Early symptoms of the disease include memory loss and confusion and can progress to disorientation, personality changes, and trouble speaking and writing. AD is the most common cause of dementia, with over 5 million people affected in the US. The prevalence of AD in the US is expected to be 13 million in 2050, with a cost of over 1 trillion dollars.

The disease manifests as two different types of excessive compounds in the brain: beta-amyloid plaques – clumps of protein that form on and around the neurons; and neurofibrillary tangles – twisted fibers of the protein tau that build up inside the neurons. Although these are the hallmarks of the disease, scientists still have much to learn about how/why they form, and how to prevent/reduce their accumulation.

Current Treatment

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There is currently no cure for Alzheimer’s, but there are various medications that can delay the progression of the disease. Treatment must be constantly monitored and adjusted because the symptoms change as the disease progresses.

The current mainstay of care is focused on enhancing the activity of acetylcholine (Ach) with medications to compensate for the lowered levels of Ach in Alzheimer’s patients. These drugs have had some benefits, particularly in the early stage of the disease, but side effects include fatigue, vomiting, loss of appetite and headache.

Potentially promising antibody therapies are often limited by their inability to efficiently cross the blood-brain barrier (BBB), a naturally occurring barrier of cells that inhibits the diffusion of drugs or toxins into the central nervous system.

Focused Ultrasound

Focused ultrasound is an new, 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. Learn how focused ultrasound works >

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 and temporarily open the BBB and enable enhanced delivery of anti-amyloid antibodies into the brain. Studies suggest that this method can reduce the number of plaques and improve cognition in preclinical Alzheimer’s disease models.

A clinical trial that repeatedly opens the BBB has been organized. This study at Sunnybrook Hospital in Toronto, Canada, uses 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. This study is only open to Canadian residents. For more information, please contact Alison Bethune ( or 416-480-6100 ext.3773)

Notable Papers

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 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.

Burgess A, Hynynen K. Noninvasive and targeted drug delivery to the brain using focused ultrasound. ACS Chem Neurosci. 2013 Apr 17;4(4):519-26.

Burgess A, Aubert I, Hynynen K. Focused ultrasound: crossing barriers to treat Alzheimer’s disease. Ther Deliv. 2011;2(3):281-6.

Click here for additional references from PubMed.

     

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