Payne, T., Appleby, M., Buckley, E. et al. (16 more authors) (2023) A double‐blind, randomized, placebo‐controlled trial of ursodeoxycholic acid (UDCA) in Parkinson's disease. Movement Disorders, 38 (8). pp. 1493-1502. ISSN 0885-3185
Abstract
Background Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD.
Objectives To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement.
Methods The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment.
Results UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups.
Conclusions High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: | 31P-MR spectroscopy; UDCA; neuroprotection; supervised gait analysis; ursodeoxycholic acid |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Funding Information: | Funder Grant number Alzheimer’s Research UK ARUK-SRF2017B-1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Jun 2023 16:00 |
Last Modified: | 03 Oct 2024 15:49 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/mds.29450 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:199907 |