"As an indirect measure of tolerability, every patient has volunteered and expressed interest in participating in the next phase."

At the 2018 Alzheimer’s Association International Conference in Chicago, Illinois, Nir Lipsman, MD, PhD, neurosurgeon at Sunnybrook Health Sciences Centre, sat down with NeurologyLive to discuss findings from a phase I, pilot, prospective trial utilizing MR-guided focused ultrasound to open the blood-brain barrier in patients with mild-to-moderate Alzheimer disease with demonstrated amyloid deposition in the targeted area.

The prospective, multi-center, single-arm study evaluated the safety and efficacy of using INSIGHTEC’s Exablate Neuro low-frequency ultrasound to disrupt the blood-brain barrier in 6 patients with early-stage Alzheimer disease.

Participants were treated twice, 1 month apart. To improve safety, the study was divided into 2 stages, graded by the volume of brain tissue for blood-brain barrier opening. The primary outcomes were clinical and radiographic outcomes, as well as the safety and technical feasibility of reversible and repeated blood-brain barrier opening. Secondary outcomes included Alzheimer-specific psychometrics, while exploratory outcomes included regional changes in [18F]-florbetaben binding on PET.

Blood-brain barrier opening was successfully achieved in all patients enrolled, demonstrating that it’s possible to focally open the blood-brain barrier in patients with Alzheimer disease in regions of the brain that are positive for amyloid, and to do so reversibly and safely, Lipsman noted.

Researchers reported no serious clinical or radiographic adverse effects or no worsening of cognitive function during the study; there were no deaths, hemorrhages, swelling or neurologic deficits on the day of procedure or throughout follow-up.

The results of the safety and feasibility study support continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer disease.

Lipsman adds that the next phase, a phase IIa trial, which will begin this fall, will study a larger group of patients to provide more comprehensive safety data as well as extensive information on radiographic biomarkers.