Sunnybrook scientists in the Hurvitz Brain Sciences Program made history this week as they non-invasively opened the blood-brain barrier (BBB) to deliver a small dose of immunotherapy directly to the brain of a patient with ALS. This is a world-first achievement.

“As with most drug therapies, the BBB limits or completely blocks access to the brain, impairing target engagement of the most promising therapeutics in patients with ALS,” says Dr. Agessandro Abrahao, co-lead investigator of the clinical trial and a neurologist in the Hurvitz Brain Sciences Program at Sunnybrook Health Sciences Centre. “For the first time in ALS, we were able to temporarily disrupt this barrier in order to allow the drug flow through.” 

On the procedure day, the first of six ALS patients received an infusion of immunoglobulin (IVIg), a potential modulator of ALS-related neuroinflammation, followed by an MRI-guided focused ultrasound procedure to open the BBB over the motor cortex on both sides of the brain.

Under the direction of Dr. Nir Lipsman, Sunnybrook’s director of the Harquail Centre for Neuromodulation and chief of the Hurvitz Brain Sciences Program, the research team used the in-house-developed Next Generation Dome Helmet to deliver focused ultrasound, guided by MR imaging. The sound waves from the Dome Helmet non-invasively and temporarily breach the BBB, allowing for the IVIg to successfully enter the brain.

Senior scientist and vice president of research and innovation at Sunnybrook Research Institute, Dr. Kullervo Hynynen, has worked with industry and Sunnybrook partners for over two decades to develop both the initial and the current Next Generation Helmet technology, and bring them to a clinic-ready state. 

“This new helmet provides enhanced image guidance, faster treatment times and targeting capacity for the investigation of personalized therapies for patients with a variety of neurological conditions and diseases of the brain,” says Dr. Hynynen, also a professor in the Department of Medical Biophysics with the Temerty Faculty of Medicine at University of Toronto. 

The use of the Dome Helmet under real-time MRI guidance in this current trial is an intermediary step in the development of an MRI-free focused ultrasound device in the future. The benefits of eliminating the need for MRI guidance would include an improved experience for patients, and overcome access and cost hurdles that come with the use of MRI.

“This world-first clinical trial highlights both the promise of focused ultrasound and the impact of technological innovation in medicine,” said Neal F. Kassell, MD, Founder and Chairman of the Focused Ultrasound Foundation. “By introducing this innovative device, we also move closer to providing accessible, personalized treatment options for ALS and other devastating brain disorders, offering new hope to patients worldwide.”

A total of six participants will be included in the first phase of the study, which is testing the safety, tolerability and preliminary biological effects of the enhanced delivery of IVIg to the brain with focused ultrasound.

“As an ALS clinician researcher, I have witnessed numerous promising therapies fail in ALS trials, but many of these drugs had limited-to-no BBB permeability and did not adequately reach the motor cortex where ALS is believed to start,” says Dr. Lorne Zinman, co-lead investigator and director of the ALS Clinic at Sunnybrook, the largest of its kind in Canada. “This innovation could be a game-changer for ALS and after future development, will significantly enhance our capacity to deliver the most promising therapeutics directly to the brain, accelerating our search for more effective treatments.”

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a neurodegenerative disorder that affects nerve cells in the brain and spinal cord. ALS causes the loss of muscle control, worsening over time and affecting one’s ability to move, eat and breathe. There is currently no cure for ALS, with patients receiving an average life expectancy of two-to-five years after diagnosis. Sunnybrook is home to the largest treatment centre for ALS in Canada.

This research is funded by the Focused Ultrasound Foundation, ALS Society of Canada, Brain Canada and the ALS Association. The research equipment is funded by the Weston Family Foundation, the WB Family Foundation, Gerald & Carla Connor, and the Temerty Foundation. The research has also received significant support from the Canadian Institutes of Health Research and National Institutes of Health.