The findings of a ground-breaking, early stage clinical trial to assess the feasibility and preliminary safety of using focused ultrasound in patients with amyotrophic lateral sclerosis (ALS) have been published in Nature Communications.
The team at Sunnybrook Health Sciences Centre in Toronto have shown that is possible to safely use MR-guided focused ultrasound to temporarily and reversibly open the blood-brain barrier (BBB) in patients with ALS.
Also known as Lou Gehrig’s disease, ALS is a degenerative motor neuron disease that affects an estimated 16,000 people in the US. As the disease progresses, the brain stops sending messages to voluntary muscles. There is no cure.
“Our research team accomplished another world-first in this study by also safely targeting the motor cortex, a part of the brain affected by ALS, with focused ultrasound,” says Agessandro Abrahao, MD, the study’s first author and investigator at Sunnybrook’s Harquail Centre for Neuromodulation. “The technology enabled us to open the BBB in this part of the brain that controls the body’s voluntary movements.”
The BBB is a protective layer of tightly joined cells that lines the blood vessels in the brain and prevents harmful substances, such as toxins and infectious agents, from diffusing into the surrounding brain tissue. It can also prevent therapeutic agents from getting into the brain, which is why research has centered on using focused ultrasound to safely and temporarily disrupt this barrier. Though no drugs were administered as part of this trial, researchers hope this early work will lead to a novel approach to deliver drugs to treat the disease in the future.
“ALS is a devastating and terminal neurological disease,” says Lorne Zinman, MD, study senior author and director of Sunnybrook’s ALS Clinic. “The successful results of this world-first trial provide an innovative way to directly and noninvasively access the brain to test the most promising ALS therapeutics to slow and one day stop disease progression.”
The Sunnybrook team is now planning a Phase II trial for ALS to expand upon these findings.
“FUS is leading edge, non-invasive technology that is a game-changer in terms of accessing areas of the brain to help treat patients like never before,” says Nir Lipsman, MD, PhD, co-author of the study and director of the Harquail Centre for Neuromodulation. “While this is an early first step, our goal is to investigate novel, direct-to-brain interventions for the most challenging brain conditions, like ALS. In the coming months, we will begin the next phase of the study which will involve the delivery of an ALS therapeutic.”
The Phase I trial was funded in part by the Focused Ultrasound Foundation.
“The Sunnybrook research team is unsurpassed at pioneering new approaches for focused ultrasound to treat a variety of challenging brain disorders,” says Neal F. Kassell, MD, Chairman of the Focused Ultrasound Foundation. “This report documents the first step in a path of clinical trials that could lead to a novel treatment for certain ALS patients, and it is leading the way for this technology to help enhance future treatment options for many patients. The Focused Ultrasound Foundation is pleased to have had the opportunity to support this trial and looks forward to participating in future research in this area.”