Toronto researchers have achieved a significant breakthrough in ALS treatment by successfully bypassing the blood-brain barrier (BBB) to deliver immunotherapy directly to affected brain regions. This world-first achievement could transform how neurodegenerative diseases are treated.
On May 9, 2025, scientists at Sunnybrook Health Sciences Centre in Toronto non-invasively opened the BBB in a patient with Amyotrophic Lateral Sclerosis (ALS), allowing targeted delivery of immunoglobulin (IVIg) therapy to the motor cortex on both sides of the brain.
"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," explains Dr. Agessandro Abrahao, co-lead investigator and neurologist in the Hurvitz Brain Sciences Program at Sunnybrook. "For the first time in ALS, we were able to temporarily disrupt this barrier in order to allow the drug flow through."
Innovative Technology Enables Targeted Drug Delivery
The groundbreaking procedure utilized the Next Generation Dome Helmet, developed in-house at Sunnybrook. This device delivers focused ultrasound waves guided by MRI to temporarily breach the BBB at specific locations, allowing the immunotherapy to enter brain regions most affected by ALS.
Dr. Nir Lipsman, Sunnybrook's director of the Harquail Centre for Neuromodulation and chief of the Hurvitz Brain Sciences Program, directed the research team during the procedure. The technology represents years of development by Dr. Kullervo Hynynen, senior scientist and vice president of research and innovation at Sunnybrook Research Institute.
"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, who is also a professor in the Department of Medical Biophysics at the University of Toronto's Temerty Faculty of Medicine.
Addressing a Critical Treatment Barrier
The BBB has long been a significant obstacle in treating neurological conditions. This protective barrier prevents harmful substances from reaching the brain but also blocks potentially beneficial medications. For ALS patients, this has meant that promising treatments often fail to reach the affected brain tissue in sufficient concentrations.
Dr. Lorne Zinman, co-lead investigator and director of Sunnybrook's ALS Clinic, highlights the significance: "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."
The current trial represents the first phase of research, focusing on safety, tolerability, and preliminary biological effects of enhanced IVIg delivery to the brain. Six participants with ALS will be included in this initial study.
Future Implications for Neurological Treatment
The current procedure requires MRI guidance, but researchers view this as an intermediary step toward developing an MRI-free focused ultrasound device. Eliminating the need for MRI would improve the patient experience while reducing access barriers and costs.
"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."
ALS: A Devastating Neurodegenerative Disease
ALS, commonly known as Lou Gehrig's disease, is a progressive neurodegenerative disorder affecting nerve cells in the brain and spinal cord. The disease causes loss of muscle control that worsens over time, affecting movement, eating, and breathing. Currently, there is no cure for ALS, and patients typically live only two to five years after diagnosis.
Sunnybrook is home to Canada's largest ALS treatment center, making it an ideal location for pioneering new approaches to this devastating condition.
The research is funded by multiple organizations including the Focused Ultrasound Foundation, ALS Society of Canada, Brain Canada, and the ALS Association, with equipment funding from the Weston Family Foundation, the WB Family Foundation, Gerald & Carla Connor, and the Temerty Foundation. Additional support comes from the Canadian Institutes of Health Research and National Institutes of Health.
If successful, this approach could revolutionize treatment not only for ALS but potentially for other neurological conditions where drug delivery is limited by the blood-brain barrier, including Alzheimer's disease, Parkinson's disease, and brain tumors.
