Grant: CIHR Fellowship

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1-2 per 1000 people. There's a need for disease-modifying therapy in PD, but many potentially effective therapeutics are limited from the brain by the blood-brain barrier. Glucocerebrosidase is an enzyme that is the standard of care for Gaucher's disease, which recently has been shown to have shared pathophysiological features with PD. Animal studies suggest replacing brain levels of glucocerebrosidase can be restorative and improve motor symptoms in PD. However, glucocerebrosidase does not cross the blood-brain barrier into the brain. An emerging way to deliver drugs past the blood-brain barrier is by creating a temporary opening using MR-guided focused ultrasound (MRgFUS). MRgFUS effectively enhances the delivery of large molecules without open surgery such as previously through direct intracranial injection. Also, MRgFUS can explicitly target the blood-brain barrier of brain regions afflicted by PD pathologies. Sunnybrook Research Institute has the world's most extensive clinical experience in MRgFUS induced opening of the blood-brain barrier. Leveraging this experience, we are taking the first-in-human step to investigate the brain delivery of recombinant glucocerebrosidase using MRgFUS in six patients with PD. The primary outcome, safety, will be described by adverse events. The feasibility of blood-brain barrier disruption will be measured by MRI with contrast, and drug delivery by cerebrospinal fluid analysis, metabolic imaging, and clinical scores. Results of this pilot study will be vital in evaluating the safety and potential of MRgFUS drug delivery platform for recombinant glucocerebrosidase. This trial will open doors for future studies in PD, neuronopathic GD, and other alpha-synucleinopathies in urgent need of disease-modifying therapy.