Cited by 429Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

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Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial

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Gauthier, Serge, Feldman, Howard H, Schneider, Lon S, Wilcock, Gordon K, Frisoni, Giovanni B, Hardlund, Jiri H, Moebius, Hans J, Bentham, Peter, Kook, Karin A, Wischik, Damon J, Schelter, Bjoern O, Davis, Charles S, Staff, Roger T, Bracoud, Luc, Shamsi, Kohkan, Storey, John M D, Harrington, Charles R, Wischik, Claude M·2016·The Lancet

DOI 10.1016/s0140-6736(16)31275-2PMC PMC5164296

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Abstract

Background Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease.Methods We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11).Findings Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31-7·34]: 75 mg LMTM twice a day [n=257] -0·02, -1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] -0·43, -2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [-8·22, 95% CI -9·63 to -6·82]: 75 mg LMTM twice a day -0·93, -3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day -0·34, -2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants.Interpretation The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon.Funding TauRx Therapeutics.

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(2015) · HAL · Cited by 2,238
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Frisoni, G. B., Fox, N. C., Jack, C. R., Scheltens, P., & Thompson, P. M. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.215 · Cited by 2,113
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Defeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676
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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
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Inestrosa, N. C., Alvarez, A. R., Pérez, C. A., Moreno, R. D., Vicente, M., Linker, C., Casanueva, O. I., Soto, C. A., & Garrido, J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80108-7 · Cited by 1,117
Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.
Wischik, C. M., Novak, M., Thøgersen, H. C., Edwards, P. C., Runswick, M. J., Jakes, R., Walker, J. E., Milstein, C., Roth, M., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.12.4506 · Cited by 939
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Braak, H., & Del Tredici, K. (2011) · Acta Neuropathologica · doi:10.1007/s00401-010-0789-4 · Cited by 812
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Maruyama, M., Shimada, H., Suhara, T., Shinotoh, H., Ji, B., Maeda, J., Zhang, M.-R., Trojanowski, J. Q., Lee, V. M.-Y., Ono, M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.037 · Cited by 760

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BackgroundSelf-citation
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“Small molecules such as methylene blue ( Figure 7) [224] and related analogs [225,226] proved to inhibit tau aggregation in vitro.”
Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs
Logroscino, G., Imbimbo, B. P., Lozupone, M., Sardone, R., Capozzo, R., Battista, P., Zecca, C., Dibello, V., Giannelli, G., Bellomo, A., et al. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1598377 · Cited by 30
Neuroprotective Approach of Anti-Cancer Microtubule Stabilizers Against Tauopathy Associated Dementia: Current Status of Clinical and Preclinical Findings
Duggal, P., & Mehan, S. (2019) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-190125 · Cited by 28
“• Blocks the polymerization of tau by trapping the tau monomers in an aggregation incompetent conformation [215, 282, 283]”
Background
Challenges in the treatment of Alzheimer’s disease: recent progress and treatment strategies of pharmaceuticals targeting notable pathological factors
Kuo, Y., & Rajesh, R. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1621750 · Cited by 27
“neuzumab against Aβ accumulation [23], increased unbound of solanezumab to Aβ42 [24], adverse gastrointestinal and urinary effects of leucomethylthioninium bis(hydromethanesulfonate) at a high dose [25], poor toleration with trends toward cognitive worsening of γ-secretase inhibitor (GSI), avagacestat at”
Background
Emerging Developments in Targeting Proteotoxicity in Neurodegenerative Diseases
McAlary, L., Plotkin, S. S., & Cashman, N. R. (2019) · CNS Drugs · doi:10.1007/s40263-019-00657-9 · Cited by 26
The Structure Biology of Tau and Clue for Aggregation Inhibitor Design
Wang, D., Huang, X., Yan, L., Zhou, L., Chang, Y., Wu, J., Su, Z., & Huang, Y. (2021) · The Protein Journal · doi:10.1007/s10930-021-10017-6 · Cited by 27
Glutamate Metabolism in Mitochondria is Closely Related to Alzheimer’s Disease
Song, J., Yang, X., Zhang, M., Wang, C., & Chen, L. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210595 · Cited by 25
Anti-amyloid: An antibody to cure Alzheimer’s or an attitude
Osborne, O., Naranjo, O., Heckmann, B. L., Dykxhoorn, D. M., & Toborek, M. J. (2023) · iScience · doi:10.1016/j.isci.2023.107461 · Cited by 25
Amyloid Pan-inhibitors: One Family of Compounds To Cope with All Conformational Diseases
Espargaró, A., Pont, C., Gámez, P., Muñoz‐Torrero, D., & Sabaté, R. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00398 · Cited by 27
Progressive Supranuclear Palsy Syndrome: An Overview
Ichikawa-Escamilla, E., Velasco-Martínez, R. A., & Adalid-Peralta, L. V. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.04.008 · Cited by 31
“Finally, the brainstem is affected in PSP-RS and PSP-PGF. clinical benefit in AD patients (Gauthier et al., 2016).”
Background
Tau Protein-Targeted Therapies in Alzheimer’s Disease: Current State and Future Perspectives
Pluta, R. M., & Ułamek-Kozioł, M. (2020) · Exon Publications eBooks · doi:10.36255/exonpublications.alzheimersdisease.2020.ch4 · Cited by 27
“The primary analysis using leuco-methylthioninium bis derivative of methylthioninium chloride in the treatment of Alzheimer’s disease was negative and the results did not suggest therapeutic benefits for Alzheimer’s disease (39).”
Method
Integrating network pharmacology, UPLC-Q–TOF–MS and molecular docking to investigate the effect and mechanism of Chuanxiong Renshen decoction against Alzheimer's disease
Shen, Z. J., Fu, Y. B., Hou, J. L., Lin, L. N., Wang, X. Y., Li, C., & Yang, Y. (2022) · Chinese Medicine · doi:10.1186/s13020-022-00698-1 · Cited by 27
“In addition, the clinical trial of leuco-methylthioninium (LMTM) and methylthioninium (MT), Tau aggregation inhibitors designed to target Tau protein, showed no significant improvement in AD [26, 27].”
Alzheimer's disease and other dementias: update on research
Schneider, L. S. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30356-8 · Cited by 25
Self-citation
“Tau immunotherapy: Hopes and hindrances”
Shahpasand, K., Shamloo, A. S., Nabavi, S. M., Lu, K. P., & Zhou, X. Z. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1393594 · Cited by 25
“was the only one to specifically assess AD treatment, and the results of this trial were negative, indicating that the use of TRx0237 small molecules in tau target therapy to treat subjects with mild-to-moderate AD was not beneficial.(42)”
Result
Neuronanomedicine for Alzheimer’s and Parkinson’s disease: Current progress and a guide to improve clinical translation
Boyton, I., Valenzuela, S. M., Collins‐Praino, L. E., & Care, A. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.11.004 · Cited by 23
Dual Targeting of Monomeric Tau and α-Synuclein Aggregation: A New Multitarget Therapeutic Strategy for Neurodegeneration
Gabr, M. T., & Peccati, F. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00281 · Cited by 24
Update on new trend and progress of the mechanism of polysaccharides in the intervention of Alzheimer's disease, based on the new understanding of relevant theories: A review
Zhang, X., Lin, L., Li, H., Xia, W., Liu, Q., Zhou, X., Lin, D., & Fu, X. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.07.158 · Cited by 25
TRPC6 mRNA levels in peripheral leucocytes of patients with Alzheimer's disease and mild cognitive impairment: A case-control study
Chen, J., Li, Q., Liu, J.-S., Jiang, G., Liu, J., Chen, S., & Cheng, Q. H. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.01.009 · Cited by 24
“By far, nearly all on-going clinical trials only recruit patients with mild AD and/or mild cognitive impairment (MCI) (Gauthier et al., 2016; Stockburger et al., 2018).”
Novel antibody against low‐n oligomers of tau protein promotes clearance of tau in cells via lysosomes
Chandupatla, R., Flatley, A., Feederle, R., Mandelkow, E., & Kaniyappan, S. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12097 · Cited by 23
Interplay Between Aging and Tau Pathology in Alzheimer’s Disease: Mechanisms and Translational Perspectives
Alrouji, M., Alshammari, M. S., Syed, T., & Shamsi, A. (2025) · Antioxidants · doi:10.3390/antiox14070774 · Cited by 21
“The effectiveness of LMTM has been evaluated in AD patients; nevertheless, the compound failed phase III clinical trials [185,186], indicating the need for more research on tau aggregation mechanisms.”
Shikonin impedes phase separation and aggregation of tau and protects SH-SY5Y cells from the toxic effects of tau oligomers
Venkatramani, A., Mukherjee, S., Kumari, A. R., & Panda, D. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.172 · Cited by 22
Resveratrol ameliorates learning and memory impairments induced by bilateral hippocampal injection of streptozotocin in mice
Wei, Y.-D., Chen, X.-X., Yang, L., Gao, X., Xia, Q., Qi, C., & Ge, J. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2022.105385 · Cited by 23
Increasing O-GlcNAcylation Attenuates tau Hyperphosphorylation and Behavioral Impairment in rTg4510 Tauopathy Mice
Rostgaard, N., Jul, P., Garmer, M., & Volbracht, C. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2205135 · Cited by 21
Preclinical, phase I, and phase II investigational clinical trials for treatment of progressive supranuclear palsy
Shoeibi, A., Olfati, N., & Litvan, I. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1460356 · Cited by 23
Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration
Yeboah, F., Kim, T., Bill, A., & Dettmer, U. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104543 · Cited by 22
Elucidating Critical Proteinopathic Mechanisms and Potential Drug Targets in Neurodegeneration
Dar, K. B., Bhat, A. H., Amin, S., Reshi, B. A., Zargar, M. A., Masood, A., & Ganie, S. A. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00741-0 · Cited by 23
Recognizing and treating atypical Parkinson disorders
Armstrong, M. J., & McFarland, N. R. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00016-9 · Cited by 24
Nicotinic acid supplementation contributes to the amelioration of Alzheimer’s disease in mouse models
Wang, Z., Zou, Z., & Li, Q. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-1148 · Cited by 21
Hyperphosphorylated Tau Inflicts Intracellular Stress Responses that Are Mitigated by Apomorphine
Song, Z., Wang, K., Hagar, H. C., Chen, H., Kuan, C.-Y., Zhang, K., & Kuo, M. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03689-x · Cited by 23
“Many natural compounds reportedly reduced AD markers including Aβ and neurofibrillary tangles in animals [43–46].”
Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice
Wang, Z., Xiong, L., Wan, W., Duan, L., Bai, X., & Zu, H. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00032 · Cited by 22
“Very recently, tau aggregation inhibitors also showed no substantial effects against memory decline in AD patients (Gauthier et al., 2016).”
Background
An evaluation of hydromethylthionine as a treatment option for Alzheimer’s disease
Hashweh, N., Bartochowski, Z., Khoury, R., & Grossberg, G. T. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1719066 · Cited by 22
“Drug name Hydromethylthionine (leuco- methylthioninium bis (hydro- methanesulfonate); LMT) Phase Phase III Indication Alzheimer’s Disease Pharmacology description Tau aggregation inhibitor Route of administration Oral Chemical structure Pivotal trial(s) NCT01626391, Gauthier et al., 2016 [41]; Wilcock et al., 2018 [42…”
Background
Human Brain Neuropharmacology: A Platform for Translational Neuroscience
Dragunow, M. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.09.002 · Cited by 23
Neuronal Vulnerability of the Entorhinal Cortex to Tau Pathology in Alzheimer’s Disease
Zhang, S., Crossley, C. A., & Yuan, Q. (2024) · British Journal of Biomedical Science · doi:10.3389/bjbs.2024.13169 · Cited by 26
Suppressing Tau Aggregation and Toxicity by an Anti-Aggregant Tau Fragment
Pir, G. J., Choudhary, B. C., Kaniyappan, S., Chandupatla, R., Mandelkow�, E., Mandelkow, E., & Wang, Y. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1326-z · Cited by 20
Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice
Li, G., Zeng, L., Cheng, H., Han, J., Zhang, X., & Xie, H. (2019) · Medical Science Monitor · doi:10.12659/msm.913858 · Cited by 20
“There are 2 main approved strategies for AD, including N-methyl-D-aspartate receptor antagonist memantine and the acetylcholinesterase inhibitors, however, both of which cannot affect the potential pathological processes and only target symptoms [5].”
Behavioural Variant Frontotemporal Dementia: Recent Advances in the Diagnosis and Understanding of the Disorder
Ahmed, R. M., Hodges, J. R., & Piguet, O. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_1 · Cited by 25
Review of evidence implicating the plasminogen activator system in blood-brain barrier dysfunction associated with Alzheimer’s disease
Tang, M.-Y., Gorin, F. A., & Lein, P. J. (2022) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2022.05 · Cited by 20
8-weeks aerobic exercise ameliorates cognitive deficit and mitigates ferroptosis triggered by iron overload in the prefrontal cortex of APPSwe/PSEN1dE9 mice through Xc−/GPx4 pathway
Li, C., Cui, K., Zhu, X., Wang, S., Yang, Q., & Fang, G. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1453582 · Cited by 22
Targeting tau protein in Alzheimer's disease
Rafii, M. S. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32107-9 · Cited by 20
Disease-modifying therapies for tauopathies: agents in the pipeline
Panza, F., Imbimbo, B. P., Lozupone, M., Greco, A., Seripa, D., Logroscino, G., Daniele, A., & Colosimo, C. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1606715 · Cited by 20
“Two 15- and 18-month Phase III RCTs of LMTM in patients with mild-to-moderate AD were negative [94].”
Background
Setbacks in Alzheimer research demand new strategies, not surrender
Jobke, B., McBride, T. C., Nevin, L. M., Peiperl, L., Ross, A. J., Stone, C., Turner, R. C., & Editors, A. T. P. M. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002518 · Cited by 20
Targeting tau in Alzheimer’s and beyond: Insights into pathology and therapeutic strategies
Singh, S., Khan, S., Shahid, M., Sardar, M., Hassan, M. I., & Islam, A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102639 · Cited by 19
Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease
Aquino, C. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.694329 · Cited by 20
“Considering the frustrating results with Aβ targeting therapies, therapeutic development in AD geared to anti-tau drugs, however, with no positive results to date (36).”
Background
Protein aggregation and neurodegenerative disease: Structural outlook for the novel therapeutics
Arar, S. H., Haque, M. A., & Kayed, R. (2023) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26561 · Cited by 20
“47,251,252 Conclusively in this direction many preclinical studies were reported to explore many synthetic and natural products including polyphenol compounds such as, curcumin and its soluble bioavailable derivatives and analogs.”
Targets, trials and tribulations in Alzheimer therapeutics
Gharat, R., Dixit, G., Khambete, M., & Prabhu, A. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.176230 · Cited by 18
Design and synthesis of multipotent 3-aminomethylindoles and 7-azaindoles with enhanced protein phosphatase 2A-activating profile and neuroprotection
Lajarín-Cuesta, R., Arribas, R. L., Nanclares, C., García‐Frutos, E. M., Gandı́a, L., & Rı́os, C. D. L. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.07.030 · Cited by 19
The protective role of endogenous n-3 polyunsaturated fatty acids inTauAlzheimer’s disease mouse model
Fang, G., Shi, B., Wu, K., Chen, S., Gao, X., Xiao, S., Kang, J. X., Li, W., & Huang, R. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1533824 · Cited by 19
“achieved good results in phase III clinical trials [16,17].”
Background

Authors: Gauthier, S., Feldman, H. H., Schneider, L. S., Wilcock, G. K., Frisoni, G. B., Hardlund, J. H., Moebius, H. J., Bentham, P., Kook, K. A., Wischik, D. J., Schelter, B. O., Davis, C. S., Staff, R. T., Bracoud, L., Shamsi, K., Storey, J. M. D., Harrington, C. R., & Wischik, C. M.
Affiliations: Douglas Mental Health University Institute (CA)
University of California San Diego (US)
University of Southern California (US)
University of Oxford (GB)
University of Geneva (CH)
TauRx (United Kingdom) (GB)
University of Aberdeen (GB)
Corresponding author: Wischik, Claude M
ORCID: Gauthier, Serge
Feldman, Howard H
Schneider, Lon S
Wilcock, Gordon K
Frisoni, Giovanni B
Moebius, Hans J
Bentham, Peter
Staff, Roger T
Bracoud, Luc
Shamsi, Kohkan
Storey, John M D
Harrington, Charles R
Venue: The Lancet
Publisher: Elsevier BV
Published: 2016-12
Volume: 388
Issue: 10062
Pages: 2873-2884
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(16)31275-2
PMC: PMC5164296
OpenAlex: W2553774099
Cited by: 427
References: 31
Citations by year: 2026: 25 · 2025: 46 · 2024: 47 · 2023: 41 · 2022: 47 · 2021: 46 · 2020: 48 · 2019: 47 · 2018: 48 · 2017: 27 · 2016: 4
FWCI: 33.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Archive ouverte UNIGE (University of Geneva) (publishedVersion)
PubMed Central (acceptedVersion)
Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders: TauRx Pharmaceuticals
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: Alzheimer's disease, tau aggregation, methylene blue, disease progression, ADAS-Cog, cognitive decline, activities of daily living, methemoglobinemia, drug safety, mild to moderate Alzheimer's disease, amyloid PET, FDG-PET
MeSH terms: Activities of Daily Living, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, tau Proteins, Treatment Failure, Mice

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Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial

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