Parkinson’s disease (PD) is a neurodegenerative condition that occurs when the brain is not able to produce dopamine, a chemical that aids in controlling movement, behaviour and cognition. PD affects more than 100,000 Canadians, and each day 30 more Canadians are diagnosed with the disease. PD impacts each individual differently, but as a progressive disease, patients’ symptoms worsen over time.
In 2022, a team of researchers at Sunnybrook Health Sciences Centre and University Health Network (UHN) led a world-first trial that used focused-ultrasound (FUS) technology to deliver a therapeutic to targeted brain regions in patients with PD.
The study, co-led by Dr. Nir Lipsman, senior scientist in the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute and director of the Harquail Centre for Neuromodulation, is now in the early stages of its second phase and will continue to explore the use of FUS for targeting therapy to both sides of the brain. Continue reading to learn more about Dr. Lipsman’s ongoing research to advance the treatment of PD.
How is FUS being used to reduce or slow down neurodegeneration in Parkinson’s disease?
Traditional PD treatments, such as dopamine replacement with medications or deep-brain stimulation, aim to improve quality of life by providing relief for specific symptoms like tremor, muscle stiffness and falling. However, they do not change the course of the disease by preventing dopamine neurons from continuing to degenerate.
One of the biggest challenges of PD treatment is that potential disease-modifying therapeutics, from gene therapy to growth factors to enzymes, are large compounds that are unable to pass through the blood-brain barrier. We’re hoping to overcome this obstacle by using MRI-guided FUS to open the blood-brain barrier in patients with PD less-invasively, so these therapies can enter and target specific parts of the brain. In our trials, we’re hoping to improve the delivery of glucocerebrosidase, an enzyme that patients with genetic and earlier-onset PD are missing.
How is the blood-brain barrier opened?
The blood-brain barrier protects the brain from toxins, but at the same time it can limit potentially beneficial medications from accessing diseased regions in the brain.
In order to open this barrier, patients are fitted with a specialized helmet, which directs ultrasound waves to precise targets in the brain which we know are important in PD. Patients are placed in an MRI for FUS treatment, where an ultrasound contrast agent, or microscopic bubbles, are injected to circulate in the bloodstream. When low-intensity FUS energy is applied, the microbubbles vibrate, temporarily expanding the space between the cells of the blood-brain barrier. This space enables a temporary opening of the blood-brain barrier and allows for direct delivery of the enzyme replacement therapy.
What potential does FUS have for treating Parkinson’s in the future?
FUS has the potential to deliver disease-modifying therapies to where it’s needed most. The ultimate goal is to find a new method of delivery for PD therapeutics that is less invasive and safe, and not only treats the challenging symptoms, but also slows the progression of the disease. By opening the blood-brain barrier, we have the ability to deliver effective therapeutics in more amounts to regions of the brain that cannot be reached with current medications and surgeries.
What stage is the trial at?
We’re still in the early stages of understanding how FUS can be used as a delivery method for PD therapeutics, and we are continuing to learn as more patients participate in the trial. In our first phase we were able to determine that the blood-brain barrier could be opened safely, reversibly and the procedure was well tolerated by patients. We are actively recruiting for the next stage of our trial, which will monitor a larger number patients as they undergo the FUS procedure multiple times. With this phase, we are hoping to further enhance the delivery of PD therapeutics.
Learn more about focused ultrasound studies for Parkinson’s disease.
