A phase 2 trial of the GSK‐3 inhibitor tideglusib in progressive supranuclear palsy
Open accessAbstract
It is believed that glycogen synthase kinase‐3 (GSK‐3) hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) study was a double‐blind, placebo‐controlled, randomized trial to assess the efficacy, safety, and tolerability of tideglusib, a GSK‐3 inhibitor, as potential treatment for PSP. The study enrolled 146 PSP patients with mild‐to‐moderate disease who were randomized to receive once‐daily 600 mg tideglusib, 800 mg tideglusib, or placebo (ratio, 2:2:1) administered orally over 52 weeks. The primary endpoint was the change from baseline to week 52 on the PSP rating scale. Secondary endpoints were safety and tolerability of tideglusib, changes in motor function (the Timed Up and Go Test), cognition (Dementia Rating Scale‐2, Frontal Assessment Battery, verbal fluency), apathy (Starkstein scale), activities of daily living (Schwab and England scale; Unified Parkinson's Disease Rating Scale, part II), quality of life (EuroQol), and Global Clinical Assessment. Brain atrophy on magnetic resonance imaging and several biomarkers in plasma and cerebrospinal fluid also were examined. No significant differences were detected in the primary or secondary endpoints at week 52 between placebo and either dose of tideglusib. Tideglusib was safe, with the exception of some asymptomatic, transient, and reversible transaminase elevations (mainly alanine aminotransferase) in 9% of patients, and diarrhea in 13% of patients. Tideglusib was generally well tolerated but it did not show clinical efficacy in patients with mild‐to‐moderate PSP. © 2014 International Parkinson and Movement Disorder Society
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In a phase II trial in patients with PSP over 52 weeks, tideglusib produced no clinical improvements.
“Another phase II trial of this drug123 was carried out in patients with PSP over 52 weeks, and no clinical improvements were observed124.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [124]
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- Authors
- Tolosa, E., Litvan, I., Höglinger, G. U., Burn, D., Lees, A., Andrés, M. V., Gómez‐Carrillo, B., León, T., del Ser, T., & for the TAUROS Investigators
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- University of California San Diego (US)
- Philipps University of Marburg (DE)
- Newcastle University (GB)
- Reta Lila Weston Institute London United Kingdom
- Clinical Department Noscira SA Madrid Spain
- Clinical Operations and Medical Affairs Department Noscira SA Madrid Spain
- Medical Department Noscira SA Madrid Spain
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2014-02-14
- Volume
- 29
- Issue
- 4
- Pages
- 470-478
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W1527750088
- Cited by
- 320
- References
- 40
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 28 · 2023: 17 · 2022: 23 · 2021: 36 · 2020: 32 · 2019: 30 · 2018: 23 · 2017: 30 · 2016: 34 · 2015: 19 · 2014: 9
- FWCI
- 19.99
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institute on Aging (R01AG024040)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- tideglusib, glycogen synthase kinase-3 inhibitors, progressive supranuclear palsy, tau hyperphosphorylation, drug efficacy, drug safety and tolerability, transaminase elevation, brain atrophy, cerebrospinal fluid biomarkers, plasma biomarkers, activities of daily living, apathy, quality of life
- MeSH terms
- Activities of Daily Living, Aged, Cognition, Double-Blind Method, Enzyme Inhibitors, Female, Humans, Male, Middle Aged, Motor Activity, Supranuclear Palsy, Progressive, Thiadiazoles, Treatment Outcome, Glycogen Synthase Kinase 3
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