Journal of Alzheimers Disease & Parkinsonism
Open Access

High-dose Ambroxol for Disease Modification and Prevention of Gba1-Related Parkinson Disease: From the Wrong Mouse to the Right Drosophila

Majdolen Istaiti^1,2*, Michal Becker-Cohen¹, Gilad Yahalom³, Shoshana Revel-Vilk^1,4, Arndt Rolfs^2,5, Mia Horowitz⁶ and Ari Zimran^1,2,4

¹Department of Neurology, Gaucher Unit, Shaare Zedek Medical Center, Jerusalem, Israel

²Department of Medicine, Agyany Pharmaceutics Ltd., Jerusalem, Israel

³Department of Neurology and Movement Disorders Clinic, Shaare Zedek Medical Center, Jerusalem, Israel

⁴Department of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

⁵Department of Neuropathology, University of Rostock, Rostock, Germany

⁶Department of Biomedicine and Cancer Research, Shmunis School of Biomedicine and Cancer Research, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel

Received Date: Nov 13, 2023 / Published Date: Dec 14, 2023

Citation: Istaiti M, Becker-Cohen M, Yahalom G, Revel-Vilk S, Rolfs A, et al. (2023) High-dose Ambroxol for Disease Modification and Prevention of Gba1-Related Parkinson Disease: From the Wrong Mouse to the Right Drosophila. J Alzheimers Dis Parkinsonism 13:588.DOI: 10.4172/2161-0460.1000588

Copyright: © 2023 Istaiti M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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After early skepticism, the association between Gaucher Disease (GD), a rare genetic disease and Parkinson's Disease (PD), the second most common neurodegenerative disorders, is well established, but its underlying mechanisms is controversial: loss of function (haploinsufficiency) or gain of function. Both approaches are supported by apparent suitable animal models. The commentary discusses the failure of substrate reduction therapy and the unlikeliness of success using enzyme replacement therapy (the loss-of-function hypothesis), and predicts future success for pharmacological chaperones, targeting the misfolded mutant glucocerebrosidase for GBA1-related PD (the gain-of-function mechanism). A unique clinical trial (AGPI) is presented, exclusively enrolling GBA1 carriers, focusing on high-dose Ambroxol in early-stage PD for both prevention and disease modification, with the hope to transform the management of GBA1-PD and related disorders.

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