Potential New Treatment for Alzheimer’s Disease
By Neal F. Kassell, MD
Founder and Chairman, Focused Ultrasound Foundation
On July 25, at the largest and most influential international meeting dedicated to advancing dementia science — the Alzheimer’s Association International Conference (AAIC) in Chicago — thousands of attendees from around the world were among the first to hear the results of a landmark clinical trial of focused ultrasound to open the blood-brain barrier (BBB) to facilitate drug therapy in patients with Alzheimer’s disease. These pilot trial results were also published today in the prestigious, high-impact journal, Nature Communications.
Nir Lipsman, MD, PhD, of Sunnybrook Health Sciences Centre in Toronto, presented the findings of this first-of-its-kind study — Blood-Brain Barrier Opening in Alzheimer’s Disease Using MR-guided Focused Ultrasound — that demonstrated the feasibility and preliminary safety of focally, reversibly and repetitively opening the BBB. This is the first small, but critically important, step in a process that could potentially lead to a novel approach to delivering drugs to the brain to treat Alzheimer’s disease.
In the study, which was organized and funded by the Focused Ultrasound Foundation and used Insightec’s Exablate Neuro device, six Alzheimer’s patients, ages 50–85, underwent two noninvasive focused ultrasound procedures. For the first stage, focused ultrasound was applied in a small area of the brain to temporarily open the BBB. In the second stage, approximately one month later, a similar procedure to the same patient targeted a larger area of the brain. No drugs were administered in the study.
The next phase will investigate the safety and efficacy of using focused ultrasound to breach the BBB in a larger group of patients with Alzheimer’s in a trial beginning this fall.
The Focused Ultrasound Foundation as a Catalyst
The brain is the vanguard target for focused ultrasound, and the therapy has been validated through rigorous scientific testing as a technology providing tremendous, transforming value to the field of functional neurosurgery. The safe and temporary opening of the BBB to deliver drugs in therapeutic concentrations to the brain is a long-sought goal for treating a wide range of neurologic conditions, including Alzheimer’s disease.
The results presented today are the culmination of years of tireless work by pioneers in the field, and they serve as an exemplary representation of the Focused Ultrasound Foundation’s role in the field.
The Foundation’s mission is to accelerate the development and adoption of focused ultrasound, and one of its high priority research areas has become Alzheimer’s disease. Over the past 6 years, the Foundation has funded research, convened researchers and physicians, and hosted workshops to explore focused ultrasound as a breakthrough therapy for the millions of Alzheimer’s patients around the world.
October 2012 — Foundation Funds Preclinical Neurodegenerative Study at Columbia University
The Foundation-funded research by Elisa Konofagou, PhD, explored the use of focused ultrasound to open the BBB to facilitate drug delivery in neurological and neurodegenerative diseases.
February 2015 — Preclinical Work to Open BBB at Sunnybrook Health Sciences Centre
Kullervo Hynynen, PhD, and his team in Toronto used focused ultrasound to open the BBB to deliver antibodies that reduce the amount of damaging plaques in the brain. They showed that repeated treatments alone (no antibodies) improved spatial memory in a mouse model of Alzheimer’s disease. This work gained the attention of NIH, and they planned to translate their findings to human clinical trials.
Dr. Hynynen presented this research during a visit to the Foundation, where we advised that his results should be replicated in a different animal model before we could consider providing funding for clinical trials.
March 2015 — Queensland Brain Institute in Australia Publishes Preclinical AD Data
Gerhard Leinenga, PhD, and Jürgen Götz, PhD, published a preclinical study in Science Translational Medicine demonstrating that combining microbubbles and ultrasound across the brain reduced the amyloid plaques in a mouse model of Alzheimer’s. They also found that treated mice had improved memory over untreated ones.
The Foundation wrote a Letter to the Editor in response to the study. With this study in mind, the Foundation felt confident to move forward in pursuing focused ultrasound as a viable tool for Alzheimer’s patients.
April 2015 — Foundation Hosts Alzheimer’s Webinar
University of Virginia Neurologist Steven T. DeKosky presented a webinar — “Alzheimer’s Disease: Introduction to Disease Pathology and Treatment” — that included discussion of focused ultrasound’s potential to impact Alzheimer’s disease treatment.
May 2015 — Foundation Forms Alzheimer’s Disease Steering Committee
The Foundation convened a Steering Committee with the goal of devising a protocol for a Phase I clinical safety and feasibility study. The Foundation’s Chief Medical Officer, Suzanne LeBlang, MD and Steven T. DeKosky, MD, Professor of Neurology Emeritus, University of Virginia School of Medicine led the group.
September 2015 — Foundation Convenes Alzheimer’s Workshop to Develop Research Roadmap
An invited group of focused ultrasound technical experts, leading Alzheimer’s neurosurgeons, neurologists, neuroscientists, neuroradiologists, and representatives from FDA, medical research foundations, and industry addressed recent breakthroughs, the existing body of work, and the challenges that must be addressed to advance toward clinical trials. Read the Summary >
May 2017 — First Alzheimer’s Trial with Focused Ultrasound Begins
The Foundation funded the world’s first clinical trial evaluating the feasibility and safety of opening the BBB in Alzheimer’s patients utilizing focused ultrasound. In all, six patients participated in the study, which was led by Nir Lipsman, MD, PhD, and researchers at Sunnybrook Health Sciences Centre in Toronto.
July 2018 — First Alzheimer’s Clinical Trial Data Published, Presented
Sunnybrook’s first-of-its-kind clinical trial data of focused ultrasound used to open the BBB in patients with Alzheimer’s disease was published in Nature Communications and presented at the Alzheimer’s Association International Conference (AAIC) in Chicago, Illinois. The study is the first peer-reviewed, published report showing the safety and feasibility of breaching the BBB in patients with Alzheimer’s disease.
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