World first: focused ultrasound opens blood-brain barrier for delivery of therapeutic in Parkinson's disease

In a groundbreaking, world-first clinical trial, a team of researchers from Sunnybrook Health Sciences Centre and University Health Network are using focused ultrasound technology to deliver a therapeutic directly to affected brain regions in patients with Parkinson’s disease (PD).

Parkinson’s affects more than 6 million people around the world. It is a brain disorder that causes tremor, rigidity, slow movement and numerous other disabling symptoms. PD is a progressive neurodegenerative disease currently without a cure, which dramatically impacts a patient’s quality of life. Each patient’s symptoms can progress at a different rate.

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

“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, the study’s co-principal investigator and Director of Sunnybrook’s Harquail Centre for Neuromodulation.

A key 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, however, are limited by their inability to cross the blood-brain barrier.

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 PD the enzyme can be defective, leading to PD symptoms. Enzyme replacement therapy is one potential strategy to reduce or prevent neurodegeneration in PD.

“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 Dr. Lorraine Kalia, co-principal investigator on the trial and a neurologist and scientist at the Krembil Brain Institute, part of University Health Network (UHN).

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.

“Parkinson’s is a progressive disease and has a debilitating impact on quality of life” explains Dr. Suneil Kalia, co-principal investigator and a neurosurgeon and scientist at UHN. “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.”

“I hope that by taking part in this clinical trial I can help make a difference,” says Pat Wilson, the first patient with PD in the world to participate in the study. “My father had Parkinson’s and I saw the difficulties he faced. I am living with the challenges of this condition, and I hope that this study can help in finding a treatment to help others with Parkinson’s in the future.”

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.

Dr. Kullervo Hynynen, Vice President of Innovation at Sunnybrook, is a pioneer in focused ultrasound. “This world-first clinical trial showcases the potential of focused ultrasound in opening the blood-brain barrier as we continue the search for new treatments that could change the course of Parkinson’s disease.”

“As one of the Focused Ultrasound Foundation’s global Centres of Excellence, Sunnybrook continues to break new ground and be a world leader in focused ultrasound – a revolutionary, noninvasive technology that has the potential to transform the treatment of Parkinson’s disease and other neurodegenerative disorders, as well as a wide variety of other life-threatening and disabling conditions,” says Neal Kassell, MD, Chairman of the Focused Ultrasound Foundation.

“This clinical trial is an exciting first step to realize the power of focused ultrasound to break down the barriers to treatment for people living with Parkinson’s disease,” says Maurice R. Ferré MD, INSIGHTEC’S CEO and Chairman of the Board of Directors.

Phase I of the trial will involve patients with a diagnosis of PD, aged 35-73 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.

A key driver of Sunnybrook’s research in focused ultrasound is philanthropic investment. This study is funded by the Focused Ultrasound Foundation, the Harquail Centre for Neuromodulation, and INSIGHTEC. UHN research is supported by the Krembil Foundation and Toronto General & Western Hospital Foundation.

For more information about this trial or focused ultrasound at Sunnybrook Health Sciences Centre, visit sunnybrook.ca/focusedultrasound

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Media contacts:

Jennifer Palisoc
Communications Advisor
jennifer.palisoc@sunnybrook.ca
416-480-4040

Heather Sherman
Sr. Public Affairs Advisor, Krembil Brain Institute
heather.sherman@uhn.ca
416-603-5294

About the Focused Ultrasound Foundation
The Focused Ultrasound Foundation was created to improve the lives of millions of people worldwide by accelerating the development of focused ultrasound, an early-stage, noninvasive, therapeutic technology with the potential to transform the treatment of many serious medical disorders. The Foundation works to clear the path to global adoption by coordinating and funding research, fostering collaboration, and building awareness among patients and professionals. It is dedicated to ensuring that focused ultrasound finds its place as a mainstream therapy for a range of conditions within years, not decades. Since its establishment in 2006, the Foundation has become the largest non-governmental source of funding for focused ultrasound research. More information can be found at fusfoundation.org.

About INSIGHTEC
INSIGHTEC is a global healthcare company creating the next generation of patient care by realizing the therapeutic power of acoustic energy. The company’s Exablate^® Neuro platform focuses sound waves, safely guided by MRI, to provide tremor relief to patients with Essential Tremor and Tremor-dominant Parkinson’s Disease. Research for future applications in the neuroscience space is underway in partnership with leading academic and medical institutions. INSIGHTEC is headquartered in Haifa, Israel, and Miami, with offices in Dallas, Shanghai and Tokyo. More information can be found at insightec.com/us/clinical/neurosurgery.

About University Health Network
University Health Network consists of Toronto General and Toronto Western Hospitals, the Princess Margaret Cancer Centre, Toronto Rehabilitation Institute, and The Michener Institute of Education at UHN. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has the largest hospital-based research program in Canada, with major research in neurosciences, surgical innovation, cardiology, transplantation, oncology, infectious diseases, genomic medicine and rehabilitation medicine. University Health Network is a research hospital affiliated with the University of Toronto. www.uhn.ca

About Sunnybrook
Sunnybrook Health Sciences Centre is inventing the future of health care for the 1.3 million patients the hospital cares for each year through the dedication of its more than 10,000 staff and volunteers. An internationally recognized leader in research and education and a full affiliation with the University of Toronto distinguishes Sunnybrook as one of Canada’s premier academic health sciences centres. Sunnybrook specializes in caring for high-risk pregnancies, critically-ill newborns and adults, offering specialized rehabilitation and treating and preventing cancer, cardiovascular disease, neurological and psychiatric disorders, orthopaedic and arthritic conditions and traumatic injuries. The Hospital also has a unique and national leading program for the care of Canada’s war veterans. www.sunnybrook.ca