Preliminary results from a clinical trial testing focused ultrasound–induced blood-brain barrier (BBB) opening with drug delivery in three patients with Alzheimer’s disease have now been published in the prestigious New England Journal of Medicine (NEJM).
The first-in-human clinical trial, led by Ali Rezai, MD, at the West Virginia University Rockefeller Neuroscience Institute (RNI), is assessing whether BBB opening in combination with a standard-of-care anti-amyloid-beta monoclonal antibody treatment can accelerate the clearance of amyloid-beta plaques in the brains of patients with Alzheimer’s disease.
The BBB is a protective layer of tightly joined cells that line the blood vessels of the brain and prevent harmful substances from entering. However, it can also prevent many therapeutic agents from getting into the brain in adequate concentrations to be effective. Focused ultrasound can be used to temporarily open the tight junctions between the cells, enabling higher concentrations of therapies to enter brain tissue.
In this trial, Dr. Rezai and his team are using Insightec’s Exablate Neuro focused ultrasound device to disrupt the BBB while patients receive monoclonal antibody therapy with aducanumab. This drug can reduce amyloid-beta plaques and slow the progression of Alzheimer’s, but it does not pass easily through the BBB. While the primary goal is to prove that the procedure is safe, researchers hope that BBB opening will allow increased concentrations of drug to reach the brain, resulting in improved reduction of the plaques that are a hallmark of Alzheimer’s disease.
The trial is off to a good start. The team has now published data from the first three participants with mild Alzheimer’s disease in the NEJM paper, “Ultrasound Blood–Brain Barrier Opening and Aducanumab in Alzheimer’s Disease.” These participants received six standard monthly infusions of aducanumab antibody therapy immediately followed by focused ultrasound–induced BBB opening in regions of the brain with high levels of amyloid-beta plaques. The procedure was safe, and there was a measurable reduction of amyloid-beta.
“After six months of antibody treatment, we observed an average of 32% more reduction in amyloid-beta plaques in brain areas with BBB opening compared to areas with no such opening,” said Dr. Rezai. “Focused ultrasound is a noninvasive outpatient procedure for BBB opening with great promise for improving drug delivery to the brain. The next phase of the clinical trial will begin this year to explore how to further accelerate amyloid-beta removal in a shorter time with focused ultrasound in combination with lecanemab antibody.”
“This is a highly important milestone in the development of focused ultrasound for treating Alzheimer’s disease by enhancing the safety and efficacy of drug delivery,” said Foundation Chairman Neal F. Kassell, MD. “The study builds on a growing body of preclinical laboratory studies and clinical trials – much of which were funded by the Foundation – and we look forward to additional research that will lead to slowing disease progression and improving cognition in patients with Alzheimer’s disease. These data also have implications for the use of focused ultrasound to augment the delivery of drugs and other therapeutic agents to the brain for treating neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, ALS, brain tumors, and more.”
For Patients
Researchers plan to enroll a total of 15 participants in this clinical trial. To learn more about enrollment, contact Padma Tirumalai, PhD, at (304) 293-4999 or ptirumalai@hsc.wvu.edu.