Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial
Abstract
It is believed that glycogen synthase kinase‐3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase‐3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double‐blind, placebo‐controlled trial in patients with mild‐to‐moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52‐week MRI. Automated, observer‐independent, atlas‐based, and mask‐based volumetry was done on high‐resolution, T1‐weighted, three‐dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: −1.3% ± 1.4% vs. −3.1% ± 2.3%, respectively), cerebrum (−1.3% ± 1.5% vs. −3.2% ± 2.1%, respectively), parietal lobe (−1.6% ± 1.9% vs. −4.1% ± 3.0%, respectively), and occipital lobe (−0.3% ± 1.8% vs. −2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society
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Clinical studies in patients with mild-to-moderate AD or PSP treated with tideglusib were negative on clinical outcomes.
“The clinical studies in patients with mild-to-moderate AD (NCT01350362, NCT00948259) or PSP (NCT01049399) patients treated with tideglusib were negative on the clinical outcomes [218]; however, a subgroup analysis of PSP patients showed reduced brain atrophy [219].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [219]
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- Authors
- Höglinger, G. U., Huppertz, H., Wagenpfeil, S., Andrés, M. V., Belloch, V., León, T., del Ser, T., & for the TAUROS MRI Investigators
- Affiliations
- Philipps University of Marburg (DE)
- Swiss Epilepsy Center (CH)
- Universitätsklinikum des Saarlandes (DE)
- Clinical Operations Department Noscira SA Madrid Spain
- Scientific Department Exploraciones Radiológicas Especiales (ERESA) Valencia Spain
- Medical Department Noscira SA Madrid Spain
- Corresponding author
- Höglinger, Günter U.
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2014-01-31
- Volume
- 29
- Issue
- 4
- Pages
- 479-487
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W1497180632
- Cited by
- 161
- References
- 27
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 5 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 14 · 2017: 19 · 2016: 18 · 2015: 13 · 2014: 13
- FWCI
- 13.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- progressive supranuclear palsy, tideglusib, glycogen synthase kinase-3 inhibition, brain atrophy, atrophy progression, tau hyperphosphorylation, volumetric MRI, parietal lobe, occipital lobe, midbrain, brainstem, cerebrum, tauopathy, neurodegenerative disease treatment
- MeSH terms
- Aged, Aged, 80 and over, Atrophy, Brain, Double-Blind Method, Enzyme Inhibitors, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Supranuclear Palsy, Progressive, Thiadiazoles, Disease Progression, Glycogen Synthase Kinase 3
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