Isabelle Aubert, PhD, is a Senior Scientist and Director of the Brain Repair Group (Aubert Laboratory) at Sunnybrook Research Institute, a Professor in the department of Laboratory Medicine and Pathobiology at the University of Toronto, and a member of the Centre of Excellence in Focused Ultrasound at Sunnybrook.
As a neurobiologist, her early work studied how ultrasound affected the brain at the cellular and molecular levels. She was thrilled to discover that ultrasound could be used to reduce pathologies related to Alzheimer’s disease and create neural regeneration in the brain. She is now exploring innovative ways to deliver therapeutic molecules to protect and repair the brain using focused ultrasound combined with microbubbles.
Over the past summer, Dr. Aubert presented one of the keynote talks, “MRI-Guided Focused Ultrasound and the Delivery of Therapeutics to the Brain,” at Drug Delivery West, an annual summit for biotechnology, pharmaceutical, and drug delivery companies to address scientific and business solutions for the best routes of delivery across different therapeutic areas with an emphasis on emerging technologies and to prepare for the future of R&D and clinical care. “Since the publication of the data from the first Alzheimer’s clinical trial at Sunnybrook, I have been asked to give more keynotes – recently in the US, Korea, and Japan – very exciting times in the field of focused ultrasound,” said Aubert. “This important safety study really changed how people view focused ultrasound. We are now getting many inquiries from companies aiming to achieve efficient delivery of their therapeutics to the brain, as well as from scientists and clinicians aspiring to move their focused ultrasound applications to the clinic.”
We interviewed Dr. Aubert to learn more about her unique approach to studying the neurobiology of focused ultrasound and how her work has been used to help patients with diseases such as Alzheimer’s, amyotrophic lateral sclerosis (ALS), and – potentially – Parkinson’s.
When and how did you get interested in focused ultrasound?
As soon as I met Dr. Kullervo Hynynen, who joined Sunnybrook Research Institute in 2006, I became fascinated by the potential of focused ultrasound to modulate the blood-brain barrier (BBB). Kullervo and I started working together right away. He had the technology, equipment, and know-how. I came from a neurobiology background, specializing in regeneration and working on therapies for neurodegenerative diseases, particularly Alzheimer’s disease. I was delivering therapeutics to the central nervous system via intracranial injection. When Kullervo arrived, I thought, “Wow, we won’t have to do these surgeries anymore! We can now access the brain non-invasively. I was equally intrigued by the plasticity of the BBB – and potentially other cells of the brain – in response to focused ultrasound.”
What is your background and what are your areas of interest in focused ultrasound?
I trained in neurobiology. From my graduate days to now, my main interest was always to find ways to stimulate brain repair and regeneration. Exploring the potential application of focused ultrasound for therapeutic delivery and brain repair was very exciting to me.
At first, I envisioned using ultrasound to deliver therapeutics to the brain. In 2010, we were successful in delivering an antibody in a mouse model of Alzheimer’s disease, and we found that amyloid pathology was reduced (Jordão, 2010). We also noticed that our control group, receiving only ultrasound combined with microbubbles for BBB permeability (no antibody) seemed to contribute to positive treatment outcomes. We expanded on the idea to increase the permeability of the BBB with no therapeutics and evaluate its effects (Jordão et al., 2013). In addition to reducing the level of amyloid beta and improving cognition, we discovered that focused ultrasound increased neurogenesis (Scarcelli et al., 2014, Burgess et al., 2014). Ultrasound and BBB modulation induced the generation of new neurons in a brain region important for learning and memory, the hippocampus. So cool! It is now exciting to figure out how this happens, and we always plan experiments with a group of mice that receives only focused ultrasound with microbubbles for BBB permeability so that we can further understand the neurobiology of focused ultrasound, build on previous discoveries, and make exciting new ones.
What mechanisms and clinical indications do you study?
My lab is studying neurodegenerative diseases and focused ultrasound—mediated BBB permeability. We are interested in the effects of focused ultrasound on brain cells, for example glia and neurons – and how to trigger molecular mechanisms that can lead to brain repair and function. As we gain depth, we are going further in the study of signaling pathways of the brain induced by ultrasound and therapeutics.
What is the goal of your work?
We aim to advance knowledge in neural plasticity, biology, and therapeutic delivery induced by focused ultrasound; and bring these fundamental discoveries to the clinic to improve the quality of life with people with brain disorders.
What are your funding sources?
Our peer-reviewed grants funding focused ultrasound work come from include agencies such as CIHR, the Western Brain Institute, the Alzheimer Society of Canada, and the Ontario Mental Health Foundation.
Meeting Report: Korean Society for Therapeutic Ultrasound September 2019
Landmark Trial Using Focused Ultrasound in Alzheimer’s Patients Presented at AAIC Meeting, Published in Nature Communications July 2018
Sunnybrook Centre of Excellence Accelerating Progress through Collaboration November 2016
Study Suggests Focused Ultrasound May Help Unlock Alzheimer’s March 2015