Opening the blood-brain barrier in Alzheimer's disease
Sunnybrook scientists made history as they used focused ultrasound to safely, non-invasively and temporarily breach the blood-brain barrier – the barrier that restricts the passage of drug treatments into the brain – in patients with Alzheimer’s disease (AD).
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Will this help me / my family member?
No, not at this time.
The goal of the Phase 2a trial is to investigate whether the blood-brain barrier (BBB) can be successfully and safely opened in people with mild/moderate stage Alzheimer’s disease (AD) using the non-invasive method of MRI-guided focused ultrasound. The areas of brain that will be targeted with ultrasound will be determined using Positron Emission Tomography (PET) brain scan imaging to display hallmarks of disease pathology, tau and amyloid deposition.
There are no medications or antibodies being administered with this trial, and the area treated is very small, so there is no expected clinical benefit to the patient.
Is this a cure for Alzheimer’s disease?
No.
The goal is that in the future, if these early stages of research are successful, that researchers may one day begin testing the feasibility and safety of injecting drug therapies or antibodies in conjunction with the opening of the BBB, and potentially move to the part of the brain that is most affected by this disease – the hub for creating new memories, called the hippocampus.
The area currently being tested is located the anterior frontal lobe of the brain which is a relatively low risk area, distant from regions of speech and motor control.
The hope is this technique may be a way to eventually, open up temporary windows into the brain to allow large molecules like drug therapies to enter. This current research discovery is the first step in this process.
What is being done at Sunnybrook?
In 2017, Sunnybrook scientists used focused ultrasound to non-invasively breach the blood-brain barrier in six patients with Alzheimer’s disease during the Phase 1 trial.
The researchers essentially created temporary openings in the barrier, which is similar to a plastic-like wrap, and observed the contrast dye enter the brain where the barrier had been opened. Ordinarily when you give a patient contrast and you scan the brain, contrast is seen only within blood vessels, and not within the brain itself.
We are fortunate at Sunnybrook to have a large interdisciplinary group of physicists, neurologists, radiologists, and neurosurgeons that collaborate to drive this pioneering work.
How did they do this? How is the BBB opened?
Through an IV in the patient’s hand or arm, the researchers inject microscopic bubbles through into the patient’s bloodstream. Smaller than red blood cells, these microbubbles enter the circulation and reach the brain, where MRI-guided low-intensity ultrasound (sound waves) is precisely targeted on small blood vessels where they want the BBB opened – in Phase 1, this was a small frontal region of the brain.
The ultrasound energy repeatedly compresses and expands the microbubbles, causing them to vibrate and gently loosen tight junctions of the cells comprising the BBB, creating a small opening.
Hasn’t this been done before?
In November 2015, Sunnybrook researchers successfully and safely opened the BBB non-invasively in a patient with brain cancer, and were able to deliver chemotherapy directly into the patient’s brain tumour for the purpose of testing. This more recent trial is the first time the BBB has been successfully and non-invasively opened in patients with Alzheimer’s disease. It was important to establish the feasibility and safety of this procedure in these patients as the changes of disease and aging may alter the structure of the blood vessels.
Implications of this research and information about the upcoming trial
While this breakthrough opens up potential in the future for testing of delivering drug therapies to parts of the brain protected by the blood brain barrier (BBB), please note that the patients (known as research participants) in the upcoming Phase 2a clinical trial will not be expected to benefit. No medications or antibodies are being introduced with this Phase 2a trial. The goal of the upcoming trial is to evaluate the procedure on a larger patient group and perform BBB opening in multiple areas of the brain that display deposits of amyloid and tau.
If the Phase 2a trial proves to be successful and safe, the future research considerations may introduce small amounts of drug therapies for testing access to parts of the brain that are most affected by this disease –those that create new memories.
Who do I contact for more information about this focused ultrasound clinical trial at Sunnybrook?
Please note:
- Enrolment in this focused ultrasound trial is limited to persons aged 50-85 years of age, and Canadian residents only, due to the inpatient hospital stay involved.
- There are no medications or antibodies being administered with this Phase 2a trial, and the area treated with ultrasound will vary with an individual’s disease and determined by PET imaging. More information on this above.
- Recruitment for this Phase 2a trial is expected to begin by October 2018.
Contact us using one of the three options:
- Fill out our online form
- Email: Allison Bethune at harquailcentre@sunnybrook.ca
- Phone: 416-480-6100 ext. 63773 (please leave your contact information)
More information:
Prevalence of Alzheimer’s disease (courtesy: Alzheimer Society of Canada)
- There are 564,000 Canadians living with dementia today.
- Each year, 25,000 more Canadians will have dementia.
- By 2031, there will be 937,000 Canadians with dementia.
- 65 per cent of Canadians with dementia over the age of 65 are women.
