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A Phase II Trial of Tideglusib in Alzheimer's Disease
Abstract
BACKGROUND: The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD). OBJECTIVE: To prove the clinical efficacy of an inhibitor of glycogen synthase kinase-3 (GSK-3), in AD. METHODS: Mild to moderate (Mini-Mental State Examination (MMSE) score, 14-26) AD patients on cholinesterase inhibitor and/or memantine treatment were administered tideglusib or placebo for 26 weeks. The ADAS-cog15 was the primary efficacy measure; function, cognition, behavior, and quality of life were assessed as secondary measures; cerebral atrophy in MRI and the levels of tau, amyloid-β, and BACE1 in cerebrospinal fluid (CSF) were exploratory endpoints. RESULTS: 306 AD patients were randomized to active (1000 mg QD: n = 86, 1000 mg QOD: n = 90, and 500 mg QD: n = 50) or placebo (n = 85) in 55 sites in four European countries. There were no statistically significant differences between either active and placebo arms in the efficacy variables. However, BACE1 in CSF significantly decreased with treatment in a small subgroup of patients. Participants with mild AD in the 500 mg QD group showed significant responses on ADAS-cog15, MMSE, and word fluency. Diarrhea (14-18% in active, 11% placebo) and dose-dependent, mild to moderate, and fully reversible transaminase increase (9-16% in active, 3.5% placebo) were the most frequent adverse events. CONCLUSIONS: Short term (26 weeks) tideglusib was acceptably safe but produced no clinical benefit in this trial. However, given the non-linear dose response, especially in mildly affected patients, further dose finding studies in early disease stages and for longer duration are warranted to examine GSK-3 inhibition in AD patients.
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In the citing paper
“Moreover, use of tau kinase inhibitors such as the GSK-3 inhibitor Tideglusib to attenuate pathological tau hyperphosphorylation also showed little or no efficacy in Phase 2 trials, probably due to the critical role of GSK-3 in multifunctional signaling pathways [650, 651].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [650]
In the citing paper
“Moreover, use of tau kinase inhibitors such as the GSK-3 inhibitor Tideglusib to attenuate pathological tau hyperphosphorylation also showed little or no efficacy in Phase 2 trials, probably due to the critical role of GSK-3 in multifunctional signaling pathways [650, 651].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [650]
In the citing paper
“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 [218]
In the citing paper
“However, a phase 2 trial in mild to moderate AD did not demonstrate any reduction in rate of cognitive or functional decline as compared to placebo (Lovestone et al., 2015)”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Lovestone et al., 2015
In the citing paper
“Tideglusib, a small-molecule GSK3β inhibitor, failed to improve cognition in a phase 2 clinical study, and CSF levels of Aβ42, total tau, and pTau181 were not altered, resulting in failure of the trial [175,176].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [176]
In the citing paper
“In a larger phase II study, tideglusib treatment was associated with significant cognitive improvement and a reduction in CSF levels of β-secretase in a subgroup of patients with mild AD122. However, when the entire study cohort was analysed, tideglusib was found to be well tolerated but produced no significant improvements122.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [122]
In the citing paper
“Another GSK-3 inhibitor, tideglusib, did not meet phase 2 clinical endpoints in patients with mild and moderate AD.80”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [80]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568
Sheikh (1986) · doi:10.1300/j018v05n01_09 · Cited by 7,236
EQ-SD: a measure of health status from the EuroQol Group
Rabin, R., & Charro, F. D. (2001) · Annals of Medicine · doi:10.3109/07853890109002087 · Cited by 5,613
The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., L. Whitwell, J., Ward, C., et al. (2008) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21049 · Cited by 4,347
A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT
Wahlund, L., Barkhof, F., Fazekas, F., Bronge, L., Augustin, M., Sjögren, M., Wallin, A., Adèr, H., Leys, D., Pantoni, L., et al. (2001) · Stroke · doi:10.1161/01.str.32.6.1318 · Cited by 1,838
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668
The glamour and gloom of glycogen synthase kinase-3
Jope, R. S., & Johnson, G. V. W. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.12.004 · Cited by 1,535
Guy, W. L. (2025) · Springer Reference Medizin · doi:10.1007/978-3-662-65186-5_300379 · Cited by 1,441
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Zhang, L., Huang, Y., Huang, W., Huang, Q., Lin, Y., & Gu, J. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261424284
Zhang, J., Li, Y., Li, Y.-P., Xun, Q., Ma, Y., & Shi, X.-L. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.109760
Vagedes, J., Hagen, A., Islam, M. O. A., Sobh, M., Vagedes, K., Szőke, H., Kohl, M., & Wilkens, J. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1758447
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Caractérisation d'anticorps à domaine unique dirigés contre la protéine Tau
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Role of T-cell immunity in the pathophysiology of Alzheimer’s disease and other Tauopathies
Matta, K. (2024) · theses.fr (ABES) · doi:10.70675/cea4fe5ez67c3z4445z92f7z39af62ba059b
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Copeland, E. N., Marais, A. A. T., Mohammad, A., Marcella, B. M., Baranowski, R. W., Beaudette, S. M., MacPherson, R. E. K., & Fajardo, V. A. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1812975
The emerging role of polo-like kinase 2 in Alzheimer's disease
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Cheng, S., Zhang, W., Zhou, J., Su, Y., Li, J., Peng, D., Liu, F., Yang, L., Pei, S., & Liu, Y. (2026) · Research Square · doi:10.21203/rs.3.rs-9640139/v1
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Chang, Y., Zhu, J., Sun, X., Wei, A., Yan, Y., Wang, H. W., & Kong, E. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44173-8.00005-x
Splicing kinases in neuronal health and neurodegeneration
El‐Gamil, D. S., Emad, M., Darwish, S. S., Hwang, T., Abadi, A. H., Engel, M., & Abdel‐Halim, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44173-8.00022-x
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Singh, A. K., Supraja, M. R., Amal, P. S., Krishnamoorthi, S., Iyaswamy, A., & Durairajan, S. S. K. (2026) · International review of neurobiology · doi:10.1016/bs.irn.2026.06.002
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Aiken, S., Zarganes‐Tzitzikas, T., & Brennan, P. E. (2026) · Essays in Biochemistry · doi:10.1042/ebc20260014
Kaur, R., Lang, D. K., Sood, A., Singh, T. G., Chandrasekaran, B., & Al-Sha’er, M. A. (2026) · RSC Advances · doi:10.1039/d6ra03269a
Rakshit, D., Nema, M., & Mishra, A. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119833
Chen, H., Zhang, L., Jiao, B., Sun, X., Guan, L., Niu, R., Li, B., Jiang, X., & Wu, Z. (2026) · Pharmaceuticals · doi:10.3390/ph19091457
Bello, L., Nwankwo, D. O., Shodehinde, S. A., Akerele, G. P., Okuntimehin, B., Ogunjobi, E. G., Awelewa, O. V., Ohilebo, A. A., Oginni, S. A., & Olubode, S. O. (2026) · Discover Chemistry. · doi:10.1007/s44371-026-00989-8
Kavitha, J., S., S. K., George, M., Francis, D., & Abi, T. G. (2026) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2026.2736169
Rewriting Phosphorylation Codes: Toward Signal-State Editing with PhosTACs
Ke, D.-T., Chang, W.-C., Chen, Y.-Y., & Chen, P. (2026) · Kinases and Phosphatases · doi:10.3390/kinasesphosphatases4040029
Unlocking therapeutic potential of Wnt signaling pathway in neurodegenerative diseases
Shah, A., Godad, A. P., & Parab, S. B. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-02006-4
BindingDB Entry 50019021: 3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents.
BindingDB (2024) · UC San Diego · doi:10.7270/q29p35xm
BindingDB (2022) · UC San Diego · doi:10.7270/q22v2kvv
BindingDB Entry 50019411: Glycogen synthase kinase-3: A potential target for diabetes.
BindingDB (2024) · UC San Diego · doi:10.7270/q2rn3d6s
BindingDB (2020) · UC San Diego · doi:10.7270/q2ng4t7x
BindingDB Entry 50000708: Natural and synthetic bioactive inhibitors of glycogen synthase kinase.
BindingDB (2019) · UC San Diego · doi:10.7270/q2cn76cn
Wnt/β-catenin signaling dysregulation in Alzheimer’s disease and therapeutic opportunities
Alkhalifa, A. E., Al-Ghraiybah, N. F., Al-Gharaibeh, A. F., & Kaddoumi, A. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.120020
Structure-based drug discovery of enzyme-inhibitor complexes using protein X-ray crystallography
Tararina, M. A., Szapiel, N., Ruzanov, M., & Kish, K. (2026) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2026.10.030
Metadata
- Authors
- Lovestone, S., for the ARGO investigators, Boada, M., Dubois, B., Hüll, M., Rinne, J. O., Huppertz, H.-J., Calero, M., Andrés, M. V., Gómez-Carrillo, B., León, T., & del Ser, T.
- Affiliations
- University of Oxford (GB)
- Fundació ACE (ES)
- Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain
- Inserm (FR)
- University of Turku (FI)
- Instituto de Salud Carlos III (ES)
- Clinical Department, Noscira SA, Madrid, Spain
- Medical Department, Noscira SA, Madrid, Spain
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2015-03-03
- Volume
- 45
- Issue
- 1
- Pages
- 75-88
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1522284801
- Cited by
- 536
- References
- 47
- Citations by year
- 2026: 44 · 2025: 67 · 2024: 59 · 2023: 46 · 2022: 38 · 2021: 59 · 2020: 61 · 2019: 31 · 2018: 46 · 2017: 39 · 2016: 31 · 2015: 14
- FWCI
- 32.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0512-10053)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- tideglusib, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Thiadiazoles, Amyloid beta-Peptides, Neuroprotective Agents
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