ALS Clinic Breakthrough, Sunnybrook Health Sciences Centre

A focused ultrasound helmet is attached to an MRI scanner as part of an early-stage clinical trial exploring the delivery of immunoglobulin to the brain of a patient with ALS at Sunnybrook Health Sciences Centre in Toronto on Wednesday, May 7, 2025. THE CANADIAN PRESS/Laura Proctor

"This is a major milestone. Now that we have the capability of opening up the blood-brain barrier to exactly target where ALS starts, I'm really excited about the future."

"ALS is a horrible, terminal, incurable neurodegenerative disease that results in the progressive decline of motor neurons in the brain and spinal cord."

"Sadly, we have about three or four deaths a week in our clinic alone, and it's awful. Literally, thousands of patients have died on my watch. And I think about that every day and how we haven't yet had major interventions to change that."

"We know that the immune system is not normal in ALS. We know that it shifts to sort of a pro-inflammatory state where the immune system is assisting in the destruction of these motor neurons."

Dr. Lorne Zinman, neurologist, director, ALS clinic, Sunnybrook Health Sciences Centre

The research team comprised of neurosurgeons, physicists from the focused ultrasound lab, ALS clinician-researchers, imaging research technicians, and anesthesiologist. Sunnybrook Research Institute

In a research trial with a 70-year-old patient who was intravenously given immunoglobulin to cross the blood-brain barrier to reach the precise area targeted by researchers there is hope that this new therapy may alleviate and outmatch the ALS process leading to premature death. Dr. Zinman is excited about the significance of the result with this experiment, searching for a therapeutic treatment for the devastating neurological disorder.

 

The 70-year-old is the first to undergo a Phase1 clinical trial to determine safety in administering drugs through non-invasive ultrasound waves to ALS patients. Five others are lined up behind this first trial, to undergo a similar trial, expanding the program. This first trial is the world's first with an ALS patient receiving a drug in this manner. The experimental procedure called focused ultrasound for patients with Alzheimer's disease and those with essential tremor, a neurological disorder causing uncontrollable shaking, was previously studied by Sunnybrook researchers.

 

"The blood-brain barrier is there to protect us, so it keeps viruses, bacteria [and] toxins outside the brain", explained neurologist and co-lead investigator of the clinical trial, Dr. Alessandro Abrahao of the Sunnybrook ALS clinic. The barrier is problematic in that it blocks access to the brain for drugs potentially treatable for ALS. The solution appears by temporarily opening the barrier to allow drugs entrance, and then closing the barrier again once the therapy has been delivered. 

 

Dallan McMahon (Research Associate) and Ryan Jones (Senior Research Engineer-Physicist) support the neurosurgeon (Dr. Nir Lipsman) in preparing for the non-invasive procedure to deliver focused ultrasound. Sunnybrook Research Institute

 

An intravenous infusion of immunoglobulin, an anti-body therapy, begins the process. Following which a helmet is placed on the patient's head, designed with 4,000 transducers to deliver focused ultrasound waves causing the microbubbles previously injected, to expand and contract in the targeted area blood vessels. The blood-brain barrier is opened by the expansions and contractions where the immunoglobulin needs to get through.

 

With helmet in place, the patient is placed within an MRI machine to enable the research team to view the focused ultrasound targeting the correct part of the brain, in real time. This, the researchers stress, is a very early-stage trial. Later stage trials with a greater number of participants will be required before a potential treatment for ALS develops. Patients diagnosed with ALS are typically given a three- to five-year survival rate. 

 

The immediate follow-up is to determine whether the immunoglobulin has had an effect, when the researchers search for biomarkers of inflammation in the patient's blood and cerebrospinal fluid.

 

Canadian researchers have launched a world-first study to fight ALS. (Sunnybrook)