4.6 Article

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

Journal

MOVEMENT DISORDERS
Volume -, Issue -, Pages -

Publisher

WILEY
DOI: 10.1002/mds.29450

Keywords

ursodeoxycholic acid; UDCA; neuroprotection; supervised gait analysis; P-31-MR spectroscopy

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The study demonstrated that high-dose UDCA is safe and well tolerated in early PD patients. P-31-MRS results showed improved ATP hydrolysis in the midbrain of the UDCA treatment group, and sensor-based gait analysis indicated possible improvement in gait parameters. Larger trials are necessary to further evaluate the disease-modifying effect of UDCA in PD.
BackgroundRescue 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. ObjectivesTo investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. MethodsThe 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 (P-31-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. ResultsUDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain P-31-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. ConclusionsHigh-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. (c) 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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