A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease.

Autor:	Payne T; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK., Appleby M; NIHR UCLH Clinical Research Facility-Leonard Wolfson Experimental Neurology Centre, National Hospital for Neurology & Neurosurgery, London, UK.; Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK., Buckley E; Department of Mechanical Engineering and Insigneo Institute for In Silico Medicine, The University of Sheffield, Sheffield, UK., van Gelder LMA; Department of Mechanical Engineering and Insigneo Institute for In Silico Medicine, The University of Sheffield, Sheffield, UK., Mullish BH; Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, St Mary's Hospital Campus, Imperial College London, London, UK., Sassani M; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK., Dunning MJ; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK.; The Bioinformatics Core, Sheffield Institute of Translational Neuroscience, University of Sheffield, Sheffield, UK., Hernandez D; Molecular Genetics Section, Laboratory of Neurogenetics, Bethesda, Maryland, USA., Scholz SW; Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, Maryland, USA., McNeill A; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK., Libri V; NIHR UCLH Clinical Research Facility-Leonard Wolfson Experimental Neurology Centre, National Hospital for Neurology & Neurosurgery, London, UK., Moll S; NIHR Sheffield Biomedical Research Centre, Royal Hallamshire Hospital, Sheffield, UK., Marchesi JR; Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, St Mary's Hospital Campus, Imperial College London, London, UK., Taylor R; Statistical Services Unit, The University of Sheffield, Sheffield, UK., Su L; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK.; Department of Psychiatry, University of Cambridge, Cambridge, UK., Mazzà C; Department of Mechanical Engineering and Insigneo Institute for In Silico Medicine, The University of Sheffield, Sheffield, UK., Jenkins TM; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK.; Royal Perth Hospital, Victoria Square, Perth, Western Australia, Australia., Foltynie T; Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK., Bandmann O; Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK.
Jazyk:	angličtina
Zdroj:	Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2023 Aug; Vol. 38 (8), pp. 1493-1502. Date of Electronic Publication: 2023 May 29.
DOI:	10.1002/mds.29450
Abstrakt:	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 ( 31 P-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 31 P-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. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze:	MEDLINE
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