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Neurodegenerative disease trials

Investigation of the Safety and Feasibility of Primary Motor Cortex Blood-Brain Barrier (BBB) Opening using Transcranial MR-Guided Focused Ultrasound with Intravenous Ultrasound Contrast Agent in Patients with Amyotrophic Lateral Sclerosis (ALS)

The goal of this study is to evaluate the safety, feasibility, and potential effectiveness of opening of the blood-brain barrier in the motor cortex with intravenous contrast agents using the ExAblate® Neuro System in patients with Amyotrophic Lateral Sclerosis (ALS). If this trial is successful in demonstrating that the motor cortex blood-brain barrier (BBB) is safely opened in patients these patients, future studies will be able to use this technique to deliver stem cells, gene therapy or large molecules to key areas of the brain of patients with ALS.

The study will be divided into two stages. In the first stage, 4 patients will undergo small volume BBB opening to establish sonication parametres. Participants will be followed for safety for 30 days. This includes evaluation of adverse effects, neurological examination and MRI scans during the treatment, and by follow-up MRI and clinical visits.

In the second stage, a larger volume BBB opening will be targeted in 4 patients, who will be assessed for any adverse effects and safety for 30 days after treatment. Follow up will also include neurological examination and MRI scans during the treatment, as well as follow-up MRI and clinical visits.

For more information or to inquire about eligibility for the trial, please contact Maheleth Llinas at harquailcentre@sunnybrook.ca.

MRgFUS in Alzheimer’s Disease Phase 1 – Study Complete

The blood-brain barrier (BBB) naturally restricts the passage of many toxins from the blood into the brain; this is protective, however it can also prevent therapies for Alzheimer’s disease (AD) from directly reaching the brain. In animal models, MR guided focused ultrasound (MRgFUS) combined with systemically injected microbubbles (MB) can non-invasively and temporarily increase BBB permeability in focal regions. Studies have shown the procedure to enhance the concentration of systemically administered anti-amyloid or anti-tau medications that target AD pathology in pre-clinical models.

In our Phase 1 study, completed in January 2018, we demonstrated the safety and feasibility of repeated MRgFUS BBB opening in a single brain region in patients with mild-to-moderate AD. Participants underwent the MRgFUS procedure twice and were followed for safety for an additional three months. Findings from this study will be published in Nature Communications later this year.

MRgFUS in Alzheimer’s Disease Phase 1/2a

In the fall of 2018 we will initiate a Phase 1/2a study to investigate the safety and feasibility of repeated MRgFUS-mediated BBB opening in multiple regions of the brain in patients in mild to moderate stages of Alzheimer’s Disease (AD).

The brain areas targeted with ultrasound will include regions displaying amyloid and tau as demonstrated on PET imaging, as well as structures implicated in memory and early involvement in AD. Exploration of cognitive test scores and clinical biomarkers in blood and Cerebrospinal Fluid (CSF) will be evaluated over the 6 months following the final ultrasound procedure. These findings will inform further trial development of MRgFUS as a tool for enhancing new drug therapies in AD.

For more information or to inquire about eligibility for the trial, please contact Allison Bethune at harquailcentre@sunnybrook.ca.