Can you tell me about your work at Sunnybrook and what you’re focusing on now?
My background is in brain plasticity and regeneration. Repairing the brain is a fascinating and challenging task. When Dr Kullervo Hynynen joined Sunnybrook Research Institute, I learned about the work that he was doing with MRI-guided focused ultrasound. I was very intrigued by the idea of bypassing the blood-brain barrier non-invasively. I discussed it with him right away, we found that we had a lot of interest in common, and we started working together.
The MRI part is to guide where you want to target the therapy in the brain. Every brain is slightly different, and with this technology, the images capture allows to precisely adjust where to direct the focused ultrasound. It’s personalized medicine regarding the localization of brain treatment. We can really target the treatment where it is needed.
It is done by first injecting microbubbles, which are phospholipid microspheres, intravenously. Then, the ultrasound goes through the cranium into the brain and the acoustic waves interact with the microbubbles in the bloodstream, the microbubbles start expanding and vibrating.
That distends the cells composing the blood-brain barrier, and the therapeutic molecules that are injected in the blood now can go through the barrier and get to the desired location in the brain.
When I realized the potential of focused ultrasound on the barrier, I thought of the many promising drugs already existing – and gene carriers with huge potential for gene therapy, that cannot effectively pass the blood-brain barrier.
And if these therapeutics had now the possibility to reach the brain, then I imagined how they could become transformative treatments.
We started testing different drugs, different gene vectors in models of Alzheimer’s disease. We had amazing effects; the most amazing discovery was the control group, just the ultrasound with the microbubbles and no drugs. That group was responding very well, almost as good as our drugtreated group.
I thought, “Wait a minute. The control conditions are really having positive effects on the brain.” We looked into it and discovered that the ultrasound alone, with the microbubbles – and no therapeutics, stimulated cells that can help in reducing brain pathology related to Alzheimer’s disease.
Indeed, a toxic molecule, called amyloid beta, was decreased. We found that some of the glial cells were reactivated, and cleaning the brain of some of these toxic molecules. We also increased neurogenesis in a part of the brain involved in learning and memory. The behavior was improved. The ultrasound with the microbubbles had therapeutic effects. This was all new. It was an “Aha” moment.
It has been over ten years since I started studying the neurobiological changes caused by blood-brain barrier modulation with focused ultrasound and microbubbles.
Now that we know about the potential of this approach for brain modulation, I’m really interested in investigating these effects further and combining them with the most promising therapeutics. Focused ultrasound with microbubbles alone is in clinical trials; we’re exploring it in people with Alzheimer’s disease, amyotrophic lateral sclerosis, and will soon start in other diseases.
It has huge promises for cancer, targeting brain tumors and allowing chemotherapeutics to reach cancer cells even in deep parts of the brain. Accessing the brain non-invasively truly offers great possibilities for treatment. People undergoing the focused ultrasound procedure are doing well.
It’s exciting to think ahead in the field of drug delivery and envision applications with the most promising therapeutics that could not get into the brain previously.
How does this affect the neurodegenerative landscape?
I think that there are infinite possibilities to explore the brain and find new ways to treat it. In neurodegenerative diseases, the brain is quite fragile already. To get some of the therapeutics into the brain, we previously had to rely on invasive intracranial surgeries.
You can imagine how much additional tissue damage there is with brain surgery to deliver a therapeutic in an already diseased brain. With focused ultrasound, the procedure is short, non-surgical, non-invasive and without requiring general anesthesia. People get fitted with the ultrasound device, receive the ultrasound treatment inside a MRI scanner and they walk out the treatment room shortly after.
You can compare and contrast open-brain surgery with being in an MRI scanner to receive an ultrasound procedure. It really improves comfort and safety.
The location of therapeutic delivery can be targeted to small or broad areas. Each brain region has different functions. It can be inhibitory or exhibitory. We have the ability for some of these diseases to tackle the neuronal circuitries at the right place, with the right therapeutics.
Your work focuses on Alzheimer’s, but could the approach be expanded out to other neurodegenerative diseases?
Yes, a similar approach can be used for other neurodegenerative disorders by tailoring it to the particular brain regions affected and using the right therapeutics. In addition to Alzheimer’s disease, this approach has potential for Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Disorders such as Friedreich’s ataxia, and mental health disorders such as depression can also benefit from the use of focused ultrasound.
Basically, focused ultrasound has potential for a wide range of brain disorders, spanning from genetic conditions requiring gene transfer to the brain, to mental health disorders and neurodegenerative diseases.
Over the course of your career, has there been any advice that you’ve given or received that you find impactful?
That’s difficult, but several thoughts come to mind. For today, I will go with “Do what you love and surround yourself with people who inspire you professionally and personally.” It made me think of a very wise advice from a great colleague. He told me: “In case of doubt, leave it out.”
Can you tell me about being an Equity, Diversity and Inclusion Officer at the University of Toronto?
My role as an EDI officer takes place as a professor at the University of Toronto, particularly in the department of Laboratory Medicine and Pathobiology (LMP).
I was always interested in helping to minimize potential biases that can happen in the process of recruitment, promotion, selection for awards, any type of advancement–for students, post-doctoral fellows and faculty.
We all have biases, our respective communities can benefit from diversity and from giving a voice and presence to all at the table. People are not always being heard or included. How can we tap into and value all of our talent when we tend to look at our standards only in a certain way?
There are several steps to be taken to increase diversity, define and promote equity and make sure we create a fair and inclusive environment. Often, you have a diverse group of people, but it’s always the same person who speaks and is listened to. What’s the point of being diverse then? We can all gain by truly listening and learning from each other.
Is there a challenging project in your career that you’re proud of how you worked to tackle it?
Initiating projects that involved perturbating the blood-brain barrier to get therapeutics into the brain was quite challenging! Over ten years ago, many in the neuroscience community told me “What are you doing? That’s too risky.”
Now, I am quite often asked “Could you test one of the therapeutic that I’m interested in and see whether it can get into the brain using ultrasound?” My answer is usually, “sure we can!” and I smile, thinking back when I received such resistance towards exploring the potential of this technology.
Keeping a mind for discovery and critical analysis
is key. We don’t know the results until we carry
the experiment and complete the analysis. As
we test our hypothesis and evaluate the safety
of the procedures, there is always a chance that
interesting unexpected findings emerge.