Dr. Michael Kaplitt of Weill Cornell Medicine, Dr. Ali Rezai of West Virginia University, and a team of researchers from the United States and Israel have released a new study that validates the use of focused ultrasound to treat patients with Alzheimer’s disease. The paper, “Noninvasive Hippocampal Blood-Brain Barrier Opening in Alzheimer's Disease With Focused Ultrasound,” reports on the successful use of low-frequency focused ultrasound for opening the blood-brain barrier at one of the deepest structures in the brain. The ability to open the blood-brain barrier there holds promise for delivering drugs, gene therapy, or other interventions to critical structures previously unreachable through the bloodstream. The paper was e-published ahead of print on April 13, 2020, by Proceedings of the National Academy of Sciences (PNAS).
The blood-brain barrier serves a protective function, preventing toxins that may be traveling in the bloodstream from crossing into the brain. This defense also prevents therapeutics from crossing the barrier, making any systemic treatments of the brain a challenge. Designing non-invasive methods for allowing selected molecules across the barrier has long been a goal of researchers seeking treatments for brain disorders.
The hippocampus and the nearby entorhinal cortex, both of which are integral to memory, are closely tied to Alzheimer’s disease. In this study, Dr. Kaplitt, Dr. Rezai, and the team of researchers injected microscopic bubbles into the bloodstream of six patients with early Alzheimer’s disease. They then directed beams of focused ultrasound from a helmet attached to an MRI scanner, which caused a temporary opening in the blood-brain barrier right at these two deep structures. The six patients underwent a total of 17 sessions of focused ultrasound, which reliably and temporarily opened the blood-brain barrier with no adverse effects. The barrier closed within 24 hours.
Dr. Kaplitt, who just a few years ago pioneered the use of high-frequency focused ultrasound for the successful treatment of essential tremor, has been researching other applications of the technology ever since. “The rapid evolution of focused ultrasound is astounding,” he says. “Our demonstration that we can safely, efficiently, and temporarily open the blood-brain barrier over most of a complex structure in the brain, without affecting any other area, may revolutionize our ability to deliver restorative therapies for brain disorders without invasive surgery.”