Tanz Centre for Research in Neurodegenerative Diseases

Focused Ultrasound Opens Blood-Brain Barrier for Parkinson's Patients

Nov 16, 2020

DR. NIR LIPSMAN, DR. LORRAINE KALIA AND DR. SUNEIL KALIADR. NIR LIPSMAN, DR. LORRAINE KALIA AND DR. SUNEIL KALIA

Researchers at the University of Toronto, Sunnybrook Health Sciences Centre and University Health Network are leading a world-first clinical trial using focused ultrasound technology to deliver a therapeutic directly to affected brain regions in patients with Parkinson’s disease.

In this study, researchers are using low intensity MRI-guided focused ultrasound to open the blood-brain barrier, which protects the brain from toxins but can also block potentially helpful medications.

Focused ultrasound harnesses the power of ultrasound waves to reach deep brain regions without the need for scalpels or cutting.

“The goal of this Phase I trial is to examine the safety of temporarily opening the blood-brain barrier in key motor regions known to be implicated in Parkinson’s disease as well as delivering promising therapeutics directly to these areas of the brain,” says Dr. Nir Lipsman, an assistant professor in the Temerty Faculty of Medicine’s Department of Surgery and Director of Sunnybrook’s Harquail Centre for Neuromodulation.

Nir Lipsman is also the study’s co-principal investigator.

Parkinson’s disease affects more than 6 million people around the world. It is a brain disorder that can cause tremor, rigidity, slow movement and numerous other disabling symptoms.

There is currently no cure for this progressive neurodegenerative disease, which dramatically impacts a patient’s quality of life.

Each patient’s symptoms can progress at a different rate.

A key hallmark of Parkinson’s 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, however, can be limited by their inability to cross the blood-brain barrier, say researchers.

Study researchers are investigating the delivery of an enzyme called glucocerebrosidase to the putamen, a key structure in the brain related to movement.

Glucocerebrosidase helps prevent buildup of alpha-synuclein but in Parkinson’s the enzyme can be defective, leading to symptoms. Enzyme replacement therapy is one potential strategy to reduce or prevent neurodegeneration in Parkinson’s.

“It’s important to remember we are still in the very early stages of this clinical trial, and while there is currently no cure for Parkinson’s, we are investigating whether using MRI-guided focused ultrasound to allow for enzyme replacement in the brain could be a promising approach to reduce or stop neurodegeneration in Parkinson’s disease,” explains co-principal investigator Dr. Lorraine Kalia, an associate professor and neurologist in the Temerty Faculty of Medicine’s Department of Medicine and co-principal investigator on the trial.

Lorraine Kalia is also a scientist at the Tanz Centre for Research in Neurodegenerative Diseases and the Krembil Brain Institute, part of University Health Network.

She says symptoms of Parkinson’s are currently managed with various therapies, treated with medication, or, in some cases, surgery. There are no available therapies to prevent neurodegeneration.

“Parkinson’s is a progressive disease and has a debilitating impact on quality of life,” explains Dr. Suneil Kalia, an associate professor and neurosurgeon in the Temerty Faculty of Medicine’s Department of Surgery and also a co-principal investigator on the trial.

Suneil Kalia is also a scientist with Krembil Brain Institute at University Health Network.

“Continued research is instrumental in the development of novel treatments. The delivery of treatments to the brain is a major hurdle we have to overcome to help patients with Parkinson’s and mitigate the progression of the disease,” he says.

In the study, low-intensity ultrasound waves target the putamen, a critical motor structure.

When ultrasound interacts with tiny-microscopic bubbles injected in the bloodstream before the treatment, the bubbles rapidly vibrate, causing a temporary opening in the blood-brain barrier.

This opening, which closes within hours of the procedure, allows the direct delivery of an enzyme replacement therapy, administered simultaneously with focused ultrasound.

Phase I of the trial will involve patients with a diagnosis of PD, aged 35 to 75 years old.

Participants will receive three doses of the therapeutic and application of focused ultrasound, every two weeks and will return for clinical imaging follow up at one, three and six months after the final focused ultrasound procedure.

The study is funded by the Focused Ultrasound Foundation, the Harquail Centre for Neuromodulation, and INSIGHTEC. University Health Network (UHN) research is supported by the Krembil Foundation and Toronto General & Western Hospital Foundation.