Under the leadership of Principal Investigator Valeria Baldivieso, MD, and Sub-Investigator Chandan Reddy, MD, MS, FAANS, the AdventHealth Research Institute is recruiting patients for the Exablate Blood-Brain Barrier (BBB) Disruption for the Treatment of Alzheimer’s Disease clinical trial (NCT03671889). This prospective, multi-center, single-arm study is evaluating the safety and efficacy of the Exablate Model 4000 Type 2.0 System (Exablate) as a tool to disrupt the blood-brain barrier in patients with probable Alzheimer's disease. AdventHealth is the first and only site in Orlando to offer this clinical trial.
Exablate uses magnetic resonance-guided focused ultrasound (MRgFUS), a minimally invasive treatment where ultrasound waves pass through the skull and brain tissues to precisely heat and ablate a deep brain target while magnetic resonance (MR) imaging allows for treatment monitoring. For this study, use of an ultrasound contrast agent causes microscopic bubbles that help Exablate direct the energy to a small region of the brain in order to temporarily disrupt the blood-brain barrier for 24-48 hours.
Through this clinical trial, patients with diagnosis of probable Alzheimer's disease may qualify to have three serial Exablate BBB disruption procedures in specific areas of the brain affected by Alzheimer’s disease to help determine whether the repeated blood-brain disruption can influence amyloid content and plaque volumes in their brains. Functional and cognitive measures will be documented as an outcome for comparison to baseline, and biomarkers will be collected from blood and spinal fluid specimens.
The Blood-Brain Barrier and its Role in Alzheimer’s Disease
A highly selective semipermeable border of endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system, the blood-brain barrier protects the brain from harmful or unwanted substances in the blood. Building off the knowledge that using focused ultrasound to disrupt the blood-brain barrier can permit noninvasive, targeted, and repeatable delivery of drugs to the brain, a recent study explored secondary effects, including augmenting immunotherapies, clearing amyloid plaques and hyperphosphorylated tau, and driving neurogenesis (generation and development of new functional neurons).
“We've known that Alzheimer's disease is a neurodegenerative disorder where there is a build-up of amyloid plaques and Tau neurofibrillary tangles in the brain, but we’ve been learning more in recent years,” shares Dr. Baldivieso. “We now know there is also inflammation happening in the brain of patients with Alzheimer’s and that there is a potential immune response in the brain that is causing that inflammation and contributing to the brain’s degeneration and atrophy. Through the Exablate BBBD study, we’re exploring whether allowing the blood-brain barrier to be open for 24 to 48 hours could safely enable the patient’s innate immune system to better recognize and attack the plaques, tangles and inflammation.”
Neurosurgeon Ali Rezai, MD, with West Virginia’s Rockefeller Neuroscience Institute, also serves as a Principal Investigator for the Exablate BBBD trial and safely completed the study procedure on 3 patients without any adverse effects. His research team found that posttreatment magnetic resonance imaging (MRI) performed on those patients revealed a unique spatiotemporal contrast enhancement pattern that suggested a perivenular immunologic healing response downstream from the targeted sites. Dr. Rezai and some of these patients were interviewed about their experience in an episode of 60 Minutes.
More About the Exablate Blood-Brain Barrier Disruption Study
The AdventHealth Research Institute is currently seeking people who meet the following criteria to participate in this study:
- Male or female, age 50-85 years
- Probable Alzheimer’s disease consistent with National Institute on Aging (NIA)/Alzheimer’s Association (AA) criteria
- Have been on a stable dose of Alzheimer’s disease medication for 3 months
- Able to communicate sensations during the Exablate procedure
- Able to attend all study visits
If all criteria are met, the patient will undergo a medical history, physical exam, lab work, imaging, and cognitive assessments for screening purposes and to establish baseline data points. Those who are deemed eligible and enroll in the study will undergo up to three Exablate procedures, approximately 14 days apart. Each procedure may take up to 4 hours. After completion of each treatment, participants will be observed for a minimum of 2 hours or until the physician feels it is safe to go home. All study participants will have 10 follow-up visits after the last ExAblate BBBD procedure: at day 7, day 8, month 1, month 3, month 6, and then once every year for 5 years.
AdventHealth’s Experience with MRgFUS
Dr. Reddy will perform all MRgFUS procedures for the Exablate BBBD study at Celebration. He has been using MRgFUS to treat movement disorders, including essential tremor and tremor-dominant Parkinson’s disease, since 2021. In the past four years, the AdventHealth Neuroscience Institute’s MRgFUS program has grown to become the largest such program in the Southeast and the second largest in the nation, recently treating its 500th patient.
“It is a precise, noninvasive technology that has provided relief and significantly improved quality of life for many of our patients with movement disorders,” says Dr. Reddy. “I’m excited to be a part of this new study to start exploring if MRgFUS could positively impact patients with Alzheimer’s Disease.”
Tackling the Challenge of Alzheimer’s Disease
Nearly 7 million Americans age 65 and older are living with Alzheimer’s, and without development of effective treatments or a cure for the disease, that number is expected to grow to 12.7 million by 2050. The U.S. Food and Drug Administration (FDA) recently approved two monoclonal antibody intravenous (IV) infusion therapies for the treatment of mild Alzheimer’s disease — lecanemab (Leqembi®) and donanemab (Kisunla™), but they come with risks and limitations.
“We now know that Alzheimer's is not just plaques and tangles in the brain, there are other mechanisms of pathology affecting the brain and contributing to development of the disease,” comments Dr. Baldivieso. “That's why we need research like the Exablate BBBD study – to help us investigate new approaches that target these mechanisms. If we identify this to be a safe, effective way to disrupt the blood-brain barrier, then we hope future research studies could explore combining BBBD with our current and perhaps even potential new Alzheimer’s medications to help slow progression of this devastating disease as we continue to work toward a cure.”
Learn more about the study at the AdventHealth Research Institute website.
