Back to Search
Start Over
Putaminal Recombinant Glucocerebrosidase Delivery with Magnetic Resonance-Guided Focused Ultrasound in Parkinson's Disease: A Phase I Study.
- Source :
-
Movement Disorders . Oct2022, Vol. 37 Issue 10, p2134-2139. 6p. - Publication Year :
- 2022
-
Abstract
- <bold>Background: </bold>GBA1 mutation is the most common genetic risk factor for Parkinson's disease (PD). Replacement of the lysosomal enzyme glucocerebrosidase (GCase) slows neurodegeneration in PD models and may be a promising disease-modifying therapy in patients with PD. However, recombinant GCase has limited penetration through the blood-brain barrier (BBB). Microbubble-mediated magnetic resonance-guided focused ultrasound (MRgFUS) can reversibly disrupt the BBB for drug delivery.<bold>Methods: </bold>This open-label phase I study investigated the safety and feasibility of MRgFUS putaminal delivery of intravenous GCase at escalating doses (15 to 30 to 60 IU/kg) every 2 weeks in four patients with PD with GBA1 mutations.<bold>Results: </bold>BBB permeability was achieved and restored in all patients as quantified by dynamic contrast-enhanced magnetic resonance imaging after treatment. There were no serious adverse events. Two patients developed transient dyskinesia after treatment. Blinded Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor scores off medication decreased by 12% at 6 months from baseline (from 26 ± 9 to 22 ± 6). Standardized uptake value ratio on fluorodeoxyglucose positron emission tomography imaging in the treated putamen reduced from 1.66 ± 0.14 to 1.27 ± 0.08.<bold>Conclusions: </bold>Results from this study demonstrate the safety and feasibility of MRgFUS GCase delivery in PD and support further investigation of this approach. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08853185
- Volume :
- 37
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Movement Disorders
- Publication Type :
- Academic Journal
- Accession number :
- 159726738
- Full Text :
- https://doi.org/10.1002/mds.29190