A new clinical trial using focused ultrasound to address Alzheimer’s disease has begun at Columbia University in New York. Researchers are investigating the safety and feasibility of using a novel focused ultrasound device in combination with microbubbles to temporarily open the blood-brain barrier (BBB) in patients with Alzheimer’s disease.
The device, developed by Elisa Konofagou, PhD, Professor of Biomedical Engineering and Radiology at Columbia University and her team, uses a single-element transducer guided by a neuronavigation system. This approach is in contrast to other focused ultrasound devices that use magnetic resonance imaging (MRI) to visualize and guide brain treatments. Dr. Konofagou successfully used the system in a preclinical study and was able to achieve clinically relevant ultrasound exposures.
“This is a unique device that can induce targeted BBB opening and confirm its location in real time based on existing MRI,” explains Dr. Konofagou. “Patients aren’t required to lie down in a MRI system during the opening. As a result, the system can be wheeled to the patient’s bedside, thereby reducing the cost and resources required for treatment as well as its total duration which can be as short as 15 to 20 minutes. This device combines the existing noninvasiveness with time-efficiency, reliability, and accessibility – qualities that are currently unavailable in other clinically tested focused ultrasound systems.”
Now, this innovative device will be tested in an FDA approved clinical trial to temporarily open the BBB. A protective layer of tightly joined cells lining the blood vessels in the brain, the BBB prevents harmful substances, such as toxins and infectious agents, from entering the brain tissue. However, it can also prevent therapeutic agents from getting into the brain and may impair the outflow of undesirable items, such as beta amyloid.
During the trial, six Alzheimer’s patients, age 50 or older, will undergo a single, noninvasive focused ultrasound procedure. Afterward, MRI and positron emission tomography (PET) scans will be used to confirm BBB opening and assess beta amyloid levels in the brain, respectively.
The accumulation of extracellular beta amyloid plaques is a distinct hallmark of the disease and is thought to be an early feature of the disease prior to cell death and tissue loss in these patients. The researchers are curious to see if opening the BBB alone – that is, without introducing a drug – will alter the levels of plaque in the brain in humans, as has been suggested by earlier preclinical research.
The trial is co-led by Dr. Konofagou and Lawrence Honig, MD, PhD, a neurologist at the Taub Institute of Alzheimer’s Disease and Aging at Columbia. The Foundation is providing funding for the study.
“If we find that our system is reliable and safe to use in Alzheimer’s patients, we will then proceed to a larger cohort to demonstrate efficacy,” says Dr. Konofagou.
“Future studies could include a pharmacological agent that will be efficacious should it be allowed to cross the ultrasound-opened BBB and reach the critical dose for therapy.”
Alzheimer’s is the most common neurodegenerative condition, and it is estimated that by 2050, more than 13 million Americans will be diagnosed with the disease. This study is the latest to try to use focused ultrasound to address the debilitating disease. Other clinical trials are ongoing or have been completed in France, Canada, and the US.
“There is a strong need for effective therapies for Alzheimer’s disease, and one issue with candidate therapies is that the BBB severely limits delivery of drugs,” says Dr. Konofagou. “The readiness of applicability of this simple system may prove pivotal as a testing platform for the most promising drugs, either new given the new opportunity of the opened barrier or existing agents that could be offered a second chance in the treatment of this devastating disease.”
Information for Patients
To be considered, patients must be age 50 or older and diagnosed with early Alzheimer's disease.
More information about this study, including additional inclusion and exclusion criteria, is available here.
Interested patients are encouraged to contact:
Elisa Konofagou, PhD
Antonios Pouliopoulos, PhD