A new clinical trial is investigating the potential of blood–brain barrier (BBB) opening as an innovative procedure in the fight against Alzheimer’s disease. The trial, being run at Ohio State University Wexner Medical Center, Weill Cornell Medicine and WVU Rockefeller Neuroscience Institute, is using non-invasive low-intensity focused ultrasound to open the BBB in patients with Alzheimer’s.
“While it’s protective and beneficial for day-to-day brain function, when we think about therapeutics, the blood–brain barrier poses a significant challenge,” says Vibhor Krishna, a neurosurgeon at Wexner Medical Center. “The focused ultrasound procedure allows us to non-invasively access the brain tissue so treatment can be administered straight to the site of pathology.”
The procedure takes place in an intraoperative MRI-surgical suite, where MR imaging guidance allows doctors to target a specific area of the brain where there is a build-up of toxic amyloid proteins, which are associated with the onset and progression of Alzheimer’s disease.
The patient’s head is immobilized in a head frame during the treatment. The ultrasound transducer elements are contained within a helmet-like device that is attached to the head frame. Surrounding the patient’s head is a water bath circulating cold, degassed water. This setup helps transmit some 1000 focused ultrasound beams through the intact skull to focus at the exact region of brain tissue that is being targeted.
During the procedure, the patient’s bloodstream is infused with microbubbles. The focused ultrasound causes these microbubbles to expand and contract, which mechanically opens the BBB. The patient is awake and alert throughout, giving real-time feedback to the treatment team. The hope is that that simply opening this barrier may help clear amyloid from the brain.
“In this research study, we are not delivering any medications,” Krishna explains. “Our hypothesis is that, by opening the blood–brain barrier, a patient’s own immune defence may clear some of those harmful amyloids. If we determine this to be safe, in the next steps we would want to understand the effectiveness and the impact of opening the blood–brain barrier in improving cognitive decline.”
Focused ultrasound opens the blood-brain barrier
The procedure is performed three times at two-week intervals to allow for as much amyloid clearance as possible. The research team will monitor the patients closely, using neurological exams and neuro-psychological exams to assess language, memory and executive functioning at various intervals for one year following the surgery. In the future, this method of opening the blood–brain barrier may also be applicable in developing new treatments for brain tumours and epilepsy.
The clinical trial, sponsored by Insightec, will enrol up to 10 patients.
