A Double‐Blind, Randomized, Placebo‐Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease
Open accessAbstract
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.
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UDCA is safe and well-tolerated in Parkinson's disease patients at a daily dose of 30 mg/kg.
“UDCA was found to be safe and well-tolerated in PD patients at a daily dose of 30 mg/kg.394”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [394]
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The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53221.x · Cited by 25,553 · see citing works
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962 · see citing works
Goetz, C. G., Tilley, B. C., Shaftman, S. R., Stebbins, G. T., Fahn, S., Martinez‐Martin, P., Poewe, W., Sampaio, C., Stern, M. B., Dodel, R., et al. (2008) · Movement Disorders · doi:10.1002/mds.22340 · Cited by 7,536 · see citing works
Systematic review of levodopa dose equivalency reporting in Parkinson's disease
Tomlinson, C. L., Stowe, R. L., Patel, S., Rick, C., Gray, R. G., & Clarke, C. E. (2010) · Movement Disorders · doi:10.1002/mds.23429 · Cited by 4,232 · see citing works
Adams, J., Dinesh, K., Xiong, M., Tarolli, C. G., Sharma, S., Sheth, N., Aranyosi, A. J., Zhu, W. Y., Goldenthal, S. B., Biglan, K., et al. (2017) · Digital Biomarkers · doi:10.1159/000479018 · Cited by 3,190 · see citing works
Mitochondrial Complex I Deficiency in Parkinson's Disease
Schapira, A. H. V., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb02325.x · Cited by 2,283 · see citing works
JENKINSON, C., FITZPATRICK, R., PETO, V., GREENHALL, R., & HYMAN, N. (1997) · Age and Ageing · doi:10.1093/ageing/26.5.353 · Cited by 1,321 · see citing works
Chaudhuri, K. R., Martinez‐Martin, P., Schapira, A. H. V., Stocchi, F., Sethi, K., Odin, P., Brown, R. G., Koller, W., Barone, P., MacPhee, G., et al. (2006) · Movement Disorders · doi:10.1002/mds.20844 · Cited by 1,100 · see citing works
Athauda, D., Maclagan, K., Skene, S. S., Bajwa-Joseph, M., Letchford, D., Chowdhury, K., Hibbert, S., Budnik, N., Zampedri, L., Dickson, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31585-4 · Cited by 889 · cited 2× · see citing works
“990778.(30) Twenty-four adverse reactions (ARs) were observed in 14/31 participants (10 UDCA and 4 placebo; Table 2).”
Self-citationEstimation of gait cycle characteristics by trunk accelerometry
Moe‐Nilssen, R., & Helbostad, J. L. (2003) · Journal of Biomechanics · doi:10.1016/s0021-9290(03)00233-1 · Cited by 641 · see citing works
Tang, R., Wei, Y., Li, Y., Chen, W., Chen, H., Wang, Q., Yang, F., Miao, Q., Xiao, X., Zhang, H., et al. (2018) · Gut · doi:10.1136/gutjnl-2016-313332 · Cited by 434 · see citing works
Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders’
Lazaridis, K. N., Gores, G. J., & Lindor, K. D. (2001) · Journal of Hepatology · doi:10.1016/s0168-8278(01)00092-7 · Cited by 420 · see citing works
Schapira, A. H. V., Olanow, C. W., Greenamyre, J. T., & Bézard, E. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61010-2 · Cited by 392 · see citing works
Brakedal, B., Dölle, C., Riemer, F., Ma, Y., Nido, G. S., SKEIE, G. O., Craven, A. R., Schwarzlmüller, T., Brekke, N., Diab, J., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.02.001 · Cited by 316 · see citing works
Goulis, J., Leandro, G., & Burroughs, A. K. (1999) · The Lancet · doi:10.1016/s0140-6736(98)11293-x · Cited by 315 · see citing works
Spain, R., George, R. J. S., Salarian, A., Mancini, M., Wagner, J. M., Horak, F. B., & BOURDETTE, D. N. (2012) · Gait & Posture · doi:10.1016/j.gaitpost.2011.11.026 · Cited by 287 · see citing works
Whone, A., Luz, M., Boca, M., Woolley, M., Mooney, L., Dharia, S., Broadfoot, J., Cronin, D., Schroers, C., Barua, N. U., et al. (2019) · Brain · doi:10.1093/brain/awz023 · Cited by 282 · see citing works
Leentjens, A. F. G., Verhey, F. R. J., Lousberg, R. L., Spitsbergen, H., & Wilmink, F. W. (2000) · International Journal of Geriatric Psychiatry · doi:10.1002/1099-1166(200007)15:7 · Cited by 280 · see citing works
Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
Borsche, M., Pereira, S. L., Klein, C., & Grünewald, A. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-201981 · Cited by 276 · see citing works
High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis
Harnois, D. M., Angulo, P., Jorgensen, R. A., LaRusso, N. F., & Lindor, K. D. (2001) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03777.x · Cited by 242 · see citing works
Gait analysis with wearables predicts conversion to Parkinson disease
Din, S. D., Elshehabi, M., Galna, B., Hobert, M. A., Warmerdam, E., Suenkel, U., Brockmann, K., Metzger, F. G., Hansen, C., Berg, D., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25548 · Cited by 211 · see citing works
Buckley, C., Alcock, L., Ardle, R. M., Rehman, R. Z. U., Din, S. D., Mazzà, C., Yarnall, A. J., & Rochester, L. (2019) · Brain Sciences · doi:10.3390/brainsci9020034 · Cited by 195 · see citing works
Self-citationPagan, F. L., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Anjum, M., Arellano, J., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4200 · Cited by 185 · see citing works
Castro-Caldas, M., Carvalho, A. N., Rodrigues, E., Henderson, C. J., Wolf, C. R., Rodrigues, C. M. P., & Gama, M. J. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8295-4 · Cited by 156 · see citing works
Simuni, T., Fiske, B., Merchant, K., Coffey, C. S., Klingner, E., Caspell-Garcia, C., Lafontant, D.-E., Matthews, H., Wyse, R. K., Brundin, P., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4725 · Cited by 149 · see citing works
Trojaniello, D., Ravaschio, A., Hausdorff, J. M., & Cereatti, A. (2015) · Gait & Posture · doi:10.1016/j.gaitpost.2015.06.008 · Cited by 146 · see citing works
Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease
Li, P., Killinger, B. A., Ensink, E., Beddows, I., Yilmaz, A., Lubben, N., Lamp, J., Schilthuis, M., Vega, I. E., Woltjer, R., et al. (2021) · Metabolites · doi:10.3390/metabo11010029 · Cited by 146 · see citing works
Cullen, S. N., Rust, C., Fleming, K., Edwards, C., Beuers, U., & Chapman, R. W. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2007.12.023 · Cited by 136 · see citing works
Mortiboys, H., Furmston, R., Bronstad, G., Aasly, J., Elliott, C., & Bandmann, O. (2015) · Neurology · doi:10.1212/wnl.0000000000001905 · Cited by 131 · see citing works
Self-citationParry, G. J., Rodrigues, C. M. P., Aranha, M. M., Hilbert, S. J., Davey, C. S., Kelkar, P., Low, W. C., & Steer, C. J. (2010) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e3181c47569 · Cited by 128 · see citing works
Abdelkader, N. F., Safar, M. M., & Salem, H. A. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9043-8 · Cited by 127 · see citing works
Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease
Mortiboys, H., Aasly, J. O., & Bandmann, O. (2013) · Brain · doi:10.1093/brain/awt224 · Cited by 124 · see citing works
Self-citationNrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson's disease
Moreira, S., Fonseca, I., Nunes, M. J., Rosa, A., Lemos, L., Rodrigues, E., Carvalho, A. N., Outeiro, T. F., Rodrigues, C. M. P., Gama, M. J., et al. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.05.009 · Cited by 112 · see citing works
Barbiroli, B., Montagna, P., Martinelli, P., Lodi, R., Iotti, S., Cortelli, P., Funicello, R., & Zaniol, P. (1993) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1993.61 · Cited by 107 · see citing works
Tauroursodeoxycholic acid improves motor symptoms in a mouse model of Parkinson's disease
Rosa, A. I., Duarte-Silva, S., Silva-Fernandes, A., Nunes, M. J., Carvalho, A. N., Rodrigues, E., Gama, M. J., Rodrigues, C. M. P., Maciel, P., & Castro-Caldas, M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1062-4 · Cited by 94 · see citing works
Henchcliffe, C., Shungu, D. C., Mao, X., Huang, C. C., Nirenberg, M. J., Jenkins, B. G., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.037 · Cited by 79 · see citing works
Qi, H., Shen, D., Jiang, C., Wang, H., & Chang, M. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135493 · Cited by 76 · see citing works
Li, H., Wang, Q., Chen, P., Zhou, C., Zhang, X., & Chen, L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.788558 · Cited by 73 · see citing works
Chun, H. S., & Low, W. C. (2011) · Toxicology · doi:10.1016/j.tox.2011.11.020 · Cited by 62 · see citing works
Progressive Gait Deficits in Parkinson’s Disease: A Wearable-Based Biannual 5-Year Prospective Study
Hobert, M. A., Nussbaum, S., Heger, T., Berg, D., Maetzler, W., & Heinzel, S. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00022 · Cited by 61 · see citing works
Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson’s Disease
Graham, S. F., Rey, N. L., Ugur, Z., Yilmaz, A., Sherman, E., Maddens, M., Bahado-Singh, R. O., Becker, K., Schulz, E., Meyerdirk, L. K., et al. (2018) · Metabolites · doi:10.3390/metabo8040071 · Cited by 60 · see citing works
Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson’s disease
Cuevas, E., Burks, S., Raymick, J., Robinson, B., Gómez-Crisóstomo, N. P., Escudero-Lourdes, C., Lopez, A. G. G., Chigurupati, S., Hanig, J., Ferguson, S. A., et al. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2020.1859729 · Cited by 57 · see citing works
Step length predicts executive dysfunction in Parkinson’s disease: a 3-year prospective study
Amboni, M., Iuppariello, L., Iavarone, A., Fasano, A. A., Palladino, R., Rucco, R., Picillo, M., Lista, I., Varriale, P., Vitale, C., et al. (2018) · Journal of Neurology · doi:10.1007/s00415-018-8973-x · Cited by 52 · see citing works
A pilot to assess target engagement of terazosin in Parkinson's disease
Schultz, J. L., Brinker, A. N., Xu, J., Ernst, S. E., Tayyari, F., Rauckhorst, A. J., Liu, L., Uc, E. Y., Taylor, E. B., Simmering, J. E., et al. (2021) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2021.11.022 · Cited by 52 · see citing works
Carling, P. J., Mortiboys, H., Green, C., Mihaylov, S. R., Sandor, C., Schwartzentruber, A., Taylor, R. N., Wei, W., Hastings, C., Wong, S. L., et al. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101772 · Cited by 49 · see citing works
Self-citationBarbiroli, B., Iotti, S., & Lodi, R. (1999) · BioFactors · doi:10.1002/biof.5520090221 · Cited by 45 · see citing works
Fighting Parkinson’s disease: The return of the mitochondria
Zambrano, K., Barba, D., Castillo, K., Noboa, L. E., Argueta-Zamora, D., Robayo, P., Arizaga, E., Caicedo, A., & Gavilanes, A. W. D. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.02.003 · Cited by 44 · see citing works
Sathe, A. G., Tuite, P., Chen, C., Ma, Y., Chen, W., Cloyd, J. C., Low, W. C., Steer, C. J., Lee, B., Zhu, X., et al. (2020) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1575 · Cited by 43 · see citing works
Micó-Amigo, M. E., Kingma, I., Heinzel, S., Rispens, S. M., Heger, T., Nussbaum, S., van Lummel, R. C., Berg, D., Maetzler, W., & van Dieën, J. H. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00059 · Cited by 42 · see citing works
Prasuhn, J., Brüggemann, N., Heßler, N., Berg, D., Gasser, T., Brockmann, K., Olbrich, D., Ziegler, A., König, I. R., Klein, C., et al. (2019) · Neurological Research and Practice · doi:10.1186/s42466-019-0033-1 · Cited by 42 · see citing works
Payne, T., Sassani, M., Buckley, E. E., Moll, S., Anton, A., Appleby, M., Maru, S., Taylor, R. N., McNeill, A., Hoggard, N., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-038911 · Cited by 33 · see citing works
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Cuadrado, A., Cazalla, E., Bach, A., Bathish, B., Naidu, S. D., DeNicola, G. M., Dinkova-Kostova, A. T., Fernández-Ginés, R., Grochot-Przeczek, A., Hayes, J. D., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103569 · Cited by 28 · see citing works
- Authors
- Payne, T., Appleby, M., Buckley, E., van Gelder, L. M. A., Mullish, B. H., Sassani, M., Dunning, M. J., Hernandez, D., Scholz, S. W., McNeill, A., Libri, V., Moll, S., Marchesi, J. R., Taylor, R., Su, L., Mazzà, C., Jenkins, T. M., Foltynie, T., & Bandmann, O.
- Affiliations
- University of Sheffield (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- Insigneo (GB)
- Department of Mechanical Engineering and Insigneo Institute for In Silico Medicine The University of Sheffield Sheffield UK
- St Mary's Hospital (GB)
- Molecular Genetics Section Laboratory of Neurogenetics Bethesda Maryland USA
- National Institutes of Health (US)
- Royal Hallamshire Hospital (GB)
- University of Cambridge (GB)
- Royal Perth Hospital (AU)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Bandmann, Oliver
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2023-05-29
- Volume
- 38
- Issue
- 8
- Pages
- 1493-1502
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC10527073
- OpenAlex
- W4378640215
- Cited by
- 76
- References
- 51
- Citations by year
- 2026: 30 · 2025: 26 · 2024: 15 · 2023: 5
- FWCI
- 12.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Movement Disorders (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by-nc-nd)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- CPT
- Jon Moulton Charity Trust
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- ursodeoxycholic acid, Parkinson's disease, mitochondrial function, neuroprotection, midbrain, 31P NMR, ATP hydrolysis, Gibbs free energy, inorganic phosphate, gait disturbance, motor progression, drug safety and tolerability, disease-modifying therapy
- MeSH terms
- Double-Blind Method, Humans, Parkinson Disease, Ursodeoxycholic Acid
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