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.

The post Redefining the delivery of Parkinson’s disease therapies: Q&A with Dr. Nir Lipsman appeared first on Your Health Matters.

For Walter Gretzky, the Great One’s dad, it was a tremor in his left hand that led to a diagnosis of Parkinson’s disease in 2012. Canadian hockey legend Wayne Gretzky recently shared news of his dad’s passing in a tweet saying, “He bravely battled Parkinson’s and other health issues these last few years, but he never let it get him down.”

What is Parkinson’s disease?

Parkinson’s disease is a progressive neurodegenerative disease that affects movement and causes tremor, stiffness, slowness and other disabling symptoms.

“Parkinson’s symptoms may progress at a different rate for each patient. Symptoms for one patient can be different than another,” says Dr. Mario Masellis, Sunnybrook neurologist in the Hurvitz Brain Sciences Program at Sunnybrook. “Parkinson’s is a debilitating disease that impacts a person’s day-to-day life. Often medication and sometimes surgery can be used to manage the symptoms of the disease but there is no cure for Parkinson’s disease.”

The exact cause of Parkinson’s is not known. Aging is one of the strongest known risk factors. Parkinson’s is caused by a combination of genetic and environmental factors, as well as a person’s age. A protein called alpha-synuclein accumulates in specific brain regions causing brain damage and ultimately loss of dopamine which results in the motor symptoms.

Each day, more than 25 people in Canada are diagnosed with Parkinson’s disease. It’s estimated that between 2011 and 2031, the number of Canadians diagnosed with Parkinson’s is expected to double to more than 163,700. Parkinson’s affects more than 6 million people around the world.

Signs and symptoms of Parkinson’s disease

There are motor and non-motor symptoms of Parkinson’s disease.

Motor symptoms are more easily visible and impact movement. Common motor symptoms for Parkinson’s include muscle stiffness or rigidity, slower movement such as walking or decreased facial expression, and tremor, which is involuntary shaking of a finger, hand or limb. Speech may also become quieter or mumbled.

Different people will experience symptoms of Parkinson’s disease in different ways. Not everyone will have tremor.

Non-motor symptoms of Parkinson’s may involve a number of changes that are not as visible including: changes to a person’s mood, depression, anxiety or problems with memory and thinking that interfere with an individual’s quality of life.

“It’s important for individuals to reach out to their health team and talk to a doctor if experiencing motor and/or non-motor symptoms of Parkinson’s disease, in particular, if the symptoms are impacting daily living and a person is not able to do their usual tasks or activity,” says Dr. Masellis.

Receiving a diagnosis could take some time. A family doctor may refer patients to a neurologist.

“The only way a patient can truly be diagnosed with Parkinson’s disease is to consult with their doctors and neurologists. A patient’s medical history will be reviewed, a physical exam will be done, and this will help doctors determine the clinical findings and appropriate diagnosis,” says Dr. Masellis.

Treatment for Parkinson’s disease

There is no cure for Parkinson’s disease and individuals can live with Parkinson’s for years. Symptoms can change over time as the disease progresses, so it is important for patients to be involved in their own treatment and care.

Medication can help manage symptoms. In some cases, surgery may be recommended to help alleviate or regulate symptoms. Exercise is important to help maintain movement and activity. Different types of therapy can be beneficial, such as physical therapy to help with mobility or speech therapy, which can help a person speak more clearly and loudly.

Innovative research is also underway to help find new ways to treat symptoms of Parkinson’s.

Dr. Masellis is leading a study at Sunnybrook that found genetic markers, which may help predict and help improve how a patient will respond to medication used to treat symptoms of Parkinson’s disease.

A world-first clinical trial recently launched by a team of researchers from Sunnybrook and University Health Network is investigating focused ultrasound technology to deliver a therapeutic directly to affect brain regions in patients with a rare genetic form of Parkinson’s disease. Focused ultrasound uses the power of sound waves to target regions of the brain without the need for cutting or scalpels.

There are many research studies underway at Sunnybrook and worldwide for Parkinson’s disease, which is among the most complex brain challenges that will be studied and treated in the new Garry Hurvitz Brain Sciences Centre, which is being built at Sunnybrook.

“Continuing research is an important step in helping patients manage Parkinson’s disease,” says Dr. Masellis. “Medications don’t always work the same way for patients with Parkinson’s disease, that’s why studying different approaches and innovations in Parkinson’s may help discover new ways of treating the disease in the future.”

The post Parkinson’s disease 101: Signs, symptoms and options for treatment appeared first on Your Health Matters.