Putaminal Recombinant Glucocerebrosidase Delivery with Magnetic Resonance–Guided Focused Ultrasound in Parkinson's Disease: A Phase I Study

• DOI: 10.1002/mds.29190
• Publication Date: 2022-09-12T06:01:07Z
• Authors: Ying Meng; Christopher B. Pople; Yuexi Huang; Ryan M. Jones; Julie Ottoy; Maged Goubran; Lais M. Oliveira; Benjamin Davidson; Liam S.P. Lawrence; Angus Z. Lau; Allison Bethune; Pejman Maralani; Agessandro Abrahao; Clement Hamani; Kullervo Hynynen; Suneil K. Kalia; Nir Lipsman; Lorraine V. Kalia
• Keywords: Movement Disorders; Putamen

GBA1 mutation is the most common genetic risk factor for Parkinson's disease (PD). Replacement of lysosomal enzyme glucocerebrosidase (GCase) slows neurodegeneration in PD models and may be a promising disease-modifying therapy patients with PD. However, recombinant GCase has limited penetration through blood-brain barrier (BBB). Microbubble-mediated magnetic resonance-guided focused ultrasound (MRgFUS) can reversibly disrupt BBB drug delivery.This open-label phase I study investigated safety feasibility MRgFUS putaminal delivery intravenous at escalating doses (15 to 30 60 IU/kg) every 2 weeks four mutations.BBB permeability was achieved restored all as quantified by dynamic contrast-enhanced resonance imaging after treatment. There were no serious adverse events. Two developed transient dyskinesia Blinded Movement Disorder Society-Unified Disease Rating Scale motor scores off medication decreased 12% 6 months from baseline (from 26 ± 9 22 6). Standardized uptake value ratio on fluorodeoxyglucose positron emission tomography treated putamen reduced 1.66 0.14 1.27 0.08.Results this demonstrate support further investigation approach. © 2022 The Authors. Disorders published Wiley Periodicals LLC behalf International Parkinson Society.