2018 Jul 31 – Magnetic resonance-guided focused ultrasound stimulation (MRgFUS) in combination with intravenously injected microbubbles has been shown to transiently increase the permeability of the blood–brain barrier (BBB) in animal models of neuropathologies, including brain tumors, Parkinson’s and Alzheimer’s disease. Nir Lipsman and coworkers of the Sunnybrook Research Center in Toronto, Canada, have now published the outcomes of the first pilot phase I trial evaluating safety and technical feasibility of this procedure in the clinics, in order to assist in the targeted delivery of therapeutic agents to selective areas in the central nervous system. The procedure was administered twice (1 month interval) to the right frontal lobe of 4 patients with early to moderate Alzheimer’s disease. Reversible BBB opening was achieved with high spatial and temporal specificity at low frequency (220 kHz) and approximately 50% power required to generate cavitation, with less than 1% of the energy used in thermal ablation. No serious clinical or radiographic adverse events were observed (deaths, hemorrhages, swelling, neurologic deficits), nor group-wise changes in levels of deposited beta-amyloid resulted from the analysis of positron emission tomography/computed tomography scans at 7 days following each sonication. Psychometric scores did not differ significantly at up to 2 months. To further current research, a phase 2a study is scheduled to begin in September on a larger sample size, targeting a more eloquent brain area in Alzheimer’s.
2019 Sep 27 – First pilot trial on 4 patients affected by amyotrofic lateral sclerosis completed at the Sunnybrook Research Center.