Ask an Expert: Drs. Lorraine and Suneil Kalia Discuss the Current Developments and Future Applications of Focused Ultrasound Technology for People with Parkinson’s
Dr. Lorraine Kalia, MD, PhD, FRCPC is a senior scientist at the Krembil Research Institute, University Health Network. She is also an associate professor in the Division of Neurology and Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto. As a neurologist, she specializes in Parkinson’s disease and related movement disorders at the Toronto Western Hospital Movement Disorders Clinic. She is also co-editor-in-chief of the Journal of Parkinson’s Disease.
Dr. Suneil Kalia, MD, PhD, FRCSC is a senior scientist at the Krembil Research Institute and KITE Research Institute, University Health Network. He is also an associate professor in the Division of Neurosurgery at the University of Toronto. As a stereotactic and functional neurosurgeon at the Toronto Western Hospital, he focuses on the surgical management of Parkinson’s disease, other movement disorders, epilepsy, and pain. He holds the R. R. Tasker Chair in Stereotactic and Functional Neurosurgery.
What is focused ultrasound technology and how does it change the brain?
Focused ultrasound (FUS) is a technology that uses a computer system and real-time imaging in a magnetic resonance imaging (MRI) machine to precisely focus and deliver ultrasound waves to any area of the brain. FUS can be either high- or low-intensity.
High-intensity FUS uses ultrasound energy to burn millimeter-sized hotspots in the brain (for example, in brain cells generating tremor). By creating small lesions in the brain, we can disrupt abnormal circuitry that is present in people with Parkinson’s, thereby reducing their tremor or other motor symptoms.
Low-intensity FUS, on the other hand, is currently investigational, and uses lower ultrasound energy to vibrate small bubbles within blood vessels to temporarily disrupt the blood-brain barrier (BBB). The BBB acts as a protective mechanism, regulating what chemicals can and cannot penetrate the brain. This is especially important, because the body can be host to many neurotoxic substances. In particular, the BBB blocks the passage of large molecules, which include many dangerous pathogens, but also unfortunately include many helpful drug therapies. By opening the BBB, low-intensity FUS can help to more effectively deliver medications and other therapeutic agents directly into brain tissue.
Presently, only high-intensity FUS is Health Canada-approved, and it is only approved for the treatment of tremor. All other applications of FUS are currently experimental.
How is FUS being used or explored as a treatment for Parkinson’s disease? What are its effects and benefits?
For Parkinson’s, high-intensity FUS may be helpful for a small sub-group of patients with tremor-dominant disease. In collaboration with the teams of Drs. Nir Lipsman and Kullervo Hynynen, we have set out to investigate low-intensity FUS to open the BBB in individuals with Parkinson’s, with the hope of delivering new drugs to slow disease progression. In our study, we aimed to deliver an active enzyme called glucocerebrosidase, which may be inactive in some people with Parkinson’s. In fact, mutations in a gene called GBA1, which encodes glucocerebrosidase, is one of the strongest genetic risk factors for developing Parkinson’s. This enzyme is already safely and routinely infused for patients with a rare neurological condition called Gaucher disease, however, it does not cross the BBB. We started by delivering this enzyme to a brain area within the basal ganglia called the putamen, which is thought to be the site where degeneration of dopamine-producing brain cells begins in those with Parkinson’s. Although our first trial focused on safety, we selected glucocerebrosidase, since there are laboratory data that suggest it may be helpful in maintaining the survival of remaining dopamine-producing brain cells. Our study described above included four people with Parkinson’s whom we treated with glucocerebrosidase using low-intensity FUS, three times each. We established that the treatments were safe and well tolerated. Our team is embarking on a new study to determine if there will be any clinical benefits or side effects in the short and long term.
What criteria would make someone with Parkinson’s an ideal candidate for FUS?
The low-intensity procedure is still under investigational study, so we cannot make any recommendations. For patients with tremor-dominant Parkinson’s, high-intensity FUS may be a treatment option but, in its current form, will not treat the other symptoms of Parkinson’s. Therefore, deep brain stimulation will be the recommended option for most people with Parkinson’s who are surgical candidates. All surgical treatments are specialized therapies requiring a multidisciplinary team. Treatment options should be reviewed with the person’s neurologist, as not everyone is a surgical candidate.
What have been some challenges you have come across in your clinical trials and how have you handled them?
Funding remains a major barrier to these trials. Our team persevered and is grateful for the support we have received from the FUS Foundation and Weston Foundation to do this work. The only option for us is to continue to advocate for people with Parkinson’s. We understand that without this type of work, the urgent need for disease-modifying therapy will not be met.
What are some potential drawbacks of this type of therapy?
In our low-intensity FUS studies, we are actively looking for possible side effects, which may include scalp numbness and headaches. We are vigilant in monitoring for any new or worsening symptoms of Parkinson’s. This work is early on the research pathway to develop new therapies for Parkinson’s, so we must first establish safety.
If trials are successful, how do you envision FUS changing the landscape of Parkinson’s disease treatments/therapies?
By providing safe and highly accurate targeting of drugs to specific areas in the brain, low-intensity FUS may allow for the advancement of disease-modifying treatments.
How accessible do you anticipate focused ultrasound technology may become for the average Parkinson’s patient?
Currently, FUS therapies for brain diseases are only available at specialized centres and must be administered by multidisciplinary teams. With telemedicine, geographical barriers could potentially be reduced, as the technology could be installed in existing MRI scanners with relative ease. However, much work still needs to be done to learn how best to use this novel technology for Parkinson’s and other diseases of the brain.
This content was published in the Spring 2023 edition of our quarterly magazine, Viewpoints. The content was accurate as of this publication date.