Researchers at Sunnybrook Health Sciences Centre in Toronto have opened the world’s very first clinical trial assessing the possibility and safety of opening the blood-brain barrier (BBB) in patients with Alzheimer’s disease (AD) applying focused ultrasound.
For this trial, 6 Alzheimer’s patients, ages 50-85, will experience two non-invasive focused ultrasound procedures. For the initial stage, Insightec’s Exablate Neuro low-frequency platform will apply focused ultrasound in a small area of the right frontal lobe, and images will assess if the BBB was briefly opened. In the succeeding stage, about one month later, a comparable procedure to the same patient will target a greater area of the right frontal lobe, and further images will again assess if the BBB is reopened. No drugs will be administered in the study.
“Our trial investigates, for the first time, the use of focused ultrasound to open the BBB in patients with early-to-moderate AD, to govern both its safety and procedural feasibility,” says Nir Lipsman, MD, co-principal investigator of the Sunnybrook study. “Results from our study will help us plan forthcoming clinical trials to establish what role focused ultrasound may play, whether alone or in combination with medical treatments, in the management of Alzheimer’s.”
Adds Sandra Black, MD, Senior Scientist and co-principal investigator at Sunnybrook, “It’s conceivable that focused ultrasound may provide a significant method for more effectively delivering antibodies to the brain and may then one day be a treatment for Alzheimer’s – we just don’t yet know. It’s important to note that at this point we are evaluating only the feasibility and safety of opening the blood-brain barrier in these patients.”
Alzheimer’s is the most common neurodegenerative condition, and it’s projected that by 2050, more than 13 million Americans will be diagnosed with AD, costing the US economy more than one trillion dollars. The buildup of extracellular beta amyloid and intracellular neurofibrillary tangles (“plaques and tangles”) are thought to be responsible for cell death and tissue loss in Alzheimer’s patients. Medical treatments to date have been only modestly effective at slowing cognitive deterioration and can only treat the symptoms.
Funded by the Focused Ultrasound Foundation, this study lays the foundation for using focused ultrasound to allow medications to reach the brain that are characteristically too large to penetrate the BBB. “An important challenge for Alzheimer’s disease therapeutics is the blood-brain barrier, which significantly restricts the passage of possibly effective therapies into the brain,” says Foundation Chairman Neal Kassell, MD. “This effort is a small but critical step in what could possibly be a game-changing treatment by improving drug delivery to the areas of the brain where they are needed, and in much higher concentrations than can be accomplished through intravenous or oral administration.”
“This is a significant breakthrough in the development of our MR-guided focused ultrasound technology,” adds Eyal Zadicario, General Manager at Insightec Israel, whose Exablate Neuro system is being utilized in the study. “Exablate Neuro was designed as a platform to support a wide range of transcranial applications and develop innovation in the neuroscience field. In the current study, Exablate Neuro is used in a new approach – to tackle neurodegenerative diseases by opening the BBB. This is just a first step, and we will continue to push the technology to make a noteworthy impact where it matters most – to patients.”
More on the trial from Sunnybrook Health Sciences Centre