title: Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate.
abstract: Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.
authors.affiliation: Department of Clinical Neurosciences, Institute of Neurology, University College London, NW3 2PF, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Migdalska-Richards
authors.affiliation: Motac Neuroscience, Manchester, United Kingdom.
authors.forename: Wai Kin D
authors.initials: WKD
authors.lastname: Ko
authors.affiliation: Motac Neuroscience, Manchester, United Kingdom.|Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing City, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Motac Neuroscience, Manchester, United Kingdom.|Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing City, People's Republic of China.|University de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, F-33000, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, F-33000, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.affiliation: Department of Clinical Neurosciences, Institute of Neurology, University College London, NW3 2PF, United Kingdom.
authors.forename: Anthony H V
authors.identifier: 0000-0002-3018-3966
authors.initials: AHV
authors.lastname: Schapira
mesh_terms: D000284:Administration, Oral; D000551:Ambroxol / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D005962:Glucosylceramidase / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D000074286:Preliminary Data; D054821:beta-Hexosaminidase beta Chain / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D000551:Ambroxol; D005962:Glucosylceramidase; D054821:beta-Hexosaminidase beta Chain
keywords: Parkinson disease; ambroxol; glucocerebrosidase; nonhuman primate