GBA-associated PD: chances and obstacles for targeted treatment strategies

Günter Höglinger; Claudia Schulte; Wolfgang H Jost; Alexander Storch; Dirk Woitalla; Rejko Krüger; Björn Falkenburger; Kathrin Brockmann

doi:10.1007/s00702-022-02511-7

GBA-associated PD: chances and obstacles for targeted treatment strategies

J Neural Transm (Vienna). 2022 Sep;129(9):1219-1233. doi: 10.1007/s00702-022-02511-7. Epub 2022 May 31.

Authors

Günter Höglinger^{1

2}, Claudia Schulte^{3

4}, Wolfgang H Jost⁵, Alexander Storch^{6

7}, Dirk Woitalla⁸, Rejko Krüger^{9

10

11}, Björn Falkenburger¹², Kathrin Brockmann^{13

14}

Affiliations

¹ Department of Neurology, Hannover Medical School, 30625, Hannover, Germany.
² German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
³ Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
⁴ German Center for Neurodegenerative Disease (DZNE), Tuebingen, Germany.
⁵ Parkinson-Klinik Ortenau, Wolfach, Germany.
⁶ Department of Neurology, Rostock University, Gehlsheimer Str. 20, 18147, Rostock, Germany.
⁷ German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Gehlsheimer Str. 20, 18147, Rostock, Germany.
⁸ Department of Neurology, St. Josef-Hospital, Katholische Kliniken Ruhrhalbinsel, Contilia Gruppe, Essen, Germany.
⁹ Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
¹⁰ Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
¹¹ Parkinson Research Clinic, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg.
¹² Department of Neurology, Faculty of Medicine, University Hospital Carl Gustav Carus and Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany.
¹³ Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. kathrin.brockmann@uni-tuebingen.de.
¹⁴ German Center for Neurodegenerative Disease (DZNE), Tuebingen, Germany. kathrin.brockmann@uni-tuebingen.de.

Abstract

Given the clear role of GBA in the pathogenesis of Parkinson's disease (PD) and its impact on phenotypical characteristics, this review provides an overview of the current knowledge of GBA-associated PD with a special focus on clinical trajectories and the underlying pathological mechanisms. Importantly, differences and characteristics based on mutation severity are recognized, and current as well as potential future treatment options are discussed. These findings will inform future strategies for patient stratification and cohort enrichment as well as suitable outcome measures when designing clinical trials.

Keywords: GBA; Lysosomal; PD; α-Synuclein.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Glucosylceramidase / genetics
Humans
Mutation
Parkinson Disease* / drug therapy
Parkinson Disease* / genetics

Substances

Glucosylceramidase