Opening the blood-brain barrier to deliver a therapeutic in Parkinson’s disease

Sunnybrook scientists have broken new ground with a clinical trial investigating the use of MRI-guided focused ultrasound (MRgFUS) in Parkinson’s Disease to safely and deliver new therapeutics by temporary opening of the blood-brain barrier (BBB).

The BBB protects the brain from toxins but at the same time limits potentially beneficial medications from accessing diseased regions the brain. This historical study explores the safety of delivering a therapeutic directly to key motor regions of the brain implicated in Parkinson’s. This study is a collaboration between Sunnybrook and University Health Network (UHN).

Interested in finding out about a referral?

Please email harquailcentre@sunnybrook.ca

Please use the email subject line: FUS Parkinson's

Learn more about focused ultrasound: sunnybrook.ca/fus

What is focused ultrasound?

Focused ultrasound is a non-invasive, image-guided surgical technology that harnesses the power of ultrasound energy. Using a specially designed helmet, ultrasound is delivered across the skull to deep brain targets without requiring scalpels or incisions. At Sunnybrook focused ultrasound is delivered in an MRI so real time image guidance can be used.

Will this help me / my family member?

The goal of the current Phase I/II trial is to expand recent findings suggesting safety opening the blood-brain barrier (BBB) in patients with Parkinson’s disease (PD) using the low-intensity MRI-guided FUS. The brain area that will be targeted with ultrasound is the putamen, an important nucleus within the basal ganglia, that plays a role in executing movement.

The study is again exploring the safety of delivering an enzyme replacement in the brain as a possible approach to reduce or slow, the neurodegenerative process in Parkinson’s disease that creates debilitating motor symptoms.

There is currently no cure for Parkinson’s.

Is this a cure for Parkinson’s disease?

No.

This current research trial is investigating the safety of injecting an enzyme in conjunction with opening the BBB in the putamen, one of the key regions of the brain implicated in Parkinson’s. The putamen is a key structure in controlling the brain’s motor circuitry.

The hope is that this technique may be a way to open temporary access ports into the brain and allow large molecules such as enzyme therapies to enter.

This Phase I/II clinical trial is a very early, but necessary step in this process.

What is being done at Sunnybrook?

In this study researchers are investigating the feasibility of delivering of an enzyme called glucocerebrosidase to the putamen using low-intensity MRI-guided focused ultrasound. Glucocerebrosidase helps prevent alpha-synuclein, an abnormal protein, from accumulating in the brain. In PD, the glucocerebrosidase enzyme can be defective, resulting in alpha-synuclein build-up, lending to impaired cell health and neurodegeneration. Enzyme replacement therapy is a potential strategy to intervene in the underlying neurodegenerative process in PD.

As this clinical trial is in early stages, the main scientific goal is to confirm safety. Researchers are probing the safety and feasibility of using MRI-guided FUS to deliver enzyme replacement. Once safety is established, investigators will aim to determine if this is a promising method to reduce or slow neurodegeneration in PD.

Symptoms of PD are currently managed with various therapies, treated with medication or in some cases surgery. There are no available therapies to prevent neurodegeneration.

How is the blood-brain barrier opened?

The patient is fitted with a specialized headframe, which directs ultrasound waves to precise targets in the brain. The patient is then placed in an MRI for the focused ultrasound treatment.

An ultrasound contrast agent, or microscopic bubbles, are injected intravenously and circulate in the bloodstream. These microbubbles are smaller than red blood cells; when low-intensity focused ultrasound energy is applied the circulating microbubbles vibrate, temporarily expanding the junctions between the cells of the BBB.

The small and temporary opening in the BBB created by focused ultrasound, allows the direct delivery of the enzyme replacement therapy. In this Phase I/II trial, the putamen is the region targeted for enzyme delivery because of its key function in Parkinson’s disease and role in motor performance.

What is the therapeutic being used in this clinical trial?

A hallmark of PD is the abnormal accumulation of a protein called alpha-synuclein in the brain which leads to unhealthy brain cells and neurodegeneration. Promising treatments to reduce alpha-synuclein accumulation exist, however, they are limited by their inability to cross the blood brain barrier. Glucocerebrosidase is an enzyme replacement that helps prevent build-up of alpha-synuclein and is approved for use in other diseases. Study researchers are investigating whether focused ultrasound can safely enhance delivery of this enzyme, providing it direct access to brain regions important in PD.

Enzyme replacement therapy is one potential strategy to reduce or prevent neurodegeneration in PD.

Who do I contact for more information about this focused ultrasound clinical trial at Sunnybrook?

Eligibility to enrol in this trial includes:

Patients with a diagnosis of Parkinson’s disease aged 35-73 years old.
Canadian residents only, due to the inpatient stay involved
Participants with known genetic status for GBA mutations will be prioritized.

Participants will receive three doses of the therapeutic enzyme, at time of FUS application, and will be followed by the study team for one year after the procedures

Contact us using one of the three options:

Fill out our online form
Email: Please use subject line: FUS Parkinson’s - harquailcentre@sunnybrook.ca
Phone: 416-480-6100 ext. 63773 (please leave your contact information)

For more information about this trial or focused ultrasound at Sunnybrook Health Sciences Centre: sunnybrook.ca/fus