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Tau-aggregation inhibitor therapy for Alzheimer's disease.
Wischik CM, Harrington CR, Storey JM. Wischik CM, et al. Biochem Pharmacol. 2014 Apr 15;88(4):529-39. doi: 10.1016/j.bcp.2013.12.008. Epub 2013 Dec 19. Biochem Pharmacol. 2014. PMID: 24361915 Free article. Review.
This truncated tau can catalyse the conversion of normal soluble tau into aggregated oligomeric and fibrillar tau which, in turn, can spread to neighbouring neurons. ...The initiation of tau aggregation requires its binding to a non-speci …
This truncated tau can catalyse the conversion of normal soluble tau into aggregated oligomeric and fibrillar tau …
Oral Tau Aggregation Inhibitor for Alzheimer's Disease: Design, Progress and Basis for Selection of the 16 mg/day Dose in a Phase 3, Randomized, Placebo-Controlled Trial of Hydromethylthionine Mesylate.
Wischik CM, Bentham P, Gauthier S, Miller S, Kook K, Schelter BO. Wischik CM, et al. J Prev Alzheimers Dis. 2022;9(4):780-790. doi: 10.14283/jpad.2022.63. J Prev Alzheimers Dis. 2022. PMID: 36281683 Free PMC article. Clinical Trial.
BACKGROUND: Hydromethylthionine mesylate is a tau aggregation inhibitor shown to have exposure-dependent pharmacological activity on cognitive decline and brain atrophy in two completed Phase 3 trials in mild/moderate Alzheimer's disease (AD). ...
BACKGROUND: Hydromethylthionine mesylate is a tau aggregation inhibitor shown to have exposure-dependent pharmacologica …
Neuroprotection of Cholinergic Neurons with a Tau Aggregation Inhibitor and Rivastigmine in an Alzheimer's-like Tauopathy Mouse Model.
Zadrozny M, Drapich P, Gasiorowska-Bien A, Niewiadomski W, Harrington CR, Wischik CM, Riedel G, Niewiadomska G. Zadrozny M, et al. Cells. 2024 Apr 6;13(7):642. doi: 10.3390/cells13070642. Cells. 2024. PMID: 38607082 Free PMC article.
Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau …
Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzhe …
Mechanisms of Anticholinesterase Interference with Tau Aggregation Inhibitor Activity in a Tau-Transgenic Mouse Model.
Riedel G, Klein J, Niewiadomska G, Kondak C, Schwab K, Lauer D, Magbagbeolu M, Steczkowska M, Zadrozny M, Wydrych M, Cranston A, Melis V, Santos RX, Theuring F, Harrington CR, Wischik CM. Riedel G, et al. Curr Alzheimer Res. 2020;17(3):285-296. doi: 10.2174/1567205017666200224120926. Curr Alzheimer Res. 2020. PMID: 32091331 Free PMC article.
In recently completed Phase 3 trials testing the tau aggregation inhibitor leuco-methylthioninium bis (hydromethanesulfonate) (LMTM), we found significant differences in treatment response according to whether patients were taking LMTM either as monotherapy o …
In recently completed Phase 3 trials testing the tau aggregation inhibitor leuco-methylthioninium bis (hydromethanesulf …
Rescue of synaptosomal glutamate release defects in tau transgenic mice by the tau aggregation inhibitor hydromethylthionine.
Cranston AL, Kraev I, Stewart MG, Horsley D, Santos RX, Robinson L, Dreesen E, Armstrong P, Palliyil S, Harrington CR, Wischik CM, Riedel G. Cranston AL, et al. Cell Signal. 2024 Sep;121:111269. doi: 10.1016/j.cellsig.2024.111269. Epub 2024 Jun 21. Cell Signal. 2024. PMID: 38909930 Free article.
The AD-like L1 model expresses the truncated core aggregation domain of the AD paired helical filament (PHF) form of tau (tau296-390) whereas the FTD-like L66 model expresses full-length tau carrying two mutations at P301S/G335D. We have used synaptosomes iso …
The AD-like L1 model expresses the truncated core aggregation domain of the AD paired helical filament (PHF) form of tau (tau2 …
Clinical, imaging and blood biomarker outcomes in a Phase 3 clinical trial of tau aggregation inhibitor hydromethylthionine mesylate in mild cognitive impairment and mild to moderate dementia due to Alzheimer's disease.
Wischik CM, Stefanacci R, Bentham P, Gauthier S, Zetterberg H, Wilcock GK, Froelich L, Burns A, MacSweeney E, Ballard C, Yu JT, Choon TS, Asvatourian V, Muehlemann N, Priel J, Kook K, Sullivan T, Downie D, Miller S, Pringle C, Storey JMD, Baddeley T, Harrington CR, Penny LK, Arastoo M, Staff R, Sandu AL, Shiells H, Lo S, Nazlee N, Evans E, Hull C, Schelter BO. Wischik CM, et al. J Prev Alzheimers Dis. 2026 Mar;13(3):100480. doi: 10.1016/j.tjpad.2026.100480. Epub 2026 Jan 21. J Prev Alzheimers Dis. 2026. PMID: 41570392 Free PMC article. Clinical Trial.
BACKGROUND: Hydromethylthionine mesylate (HMTM) targets tau pathology and has tau-independent symptomatic activity. OBJECTIVES: To evaluate the safety and efficacy of HMTM in participants with mild cognitive impairment (MCI) and mild to moderate dementia due to Alzh …
BACKGROUND: Hydromethylthionine mesylate (HMTM) targets tau pathology and has tau-independent symptomatic activity. OBJECTIVES …
Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease.
Wischik CM, Staff RT, Wischik DJ, Bentham P, Murray AD, Storey JM, Kook KA, Harrington CR. Wischik CM, et al. J Alzheimers Dis. 2015;44(2):705-20. doi: 10.3233/JAD-142874. J Alzheimers Dis. 2015. PMID: 25550228 Free article. Clinical Trial.
BACKGROUND: As tau aggregation pathology correlates with clinical dementia in Alzheimer's disease (AD), a tau aggregation inhibitor (TAI) could have therapeutic utility. Methylthioninium (MT) acts as a selective TAI in vitro and reduces tau …
BACKGROUND: As tau aggregation pathology correlates with clinical dementia in Alzheimer's disease (AD), a tau aggreg …
Assays for the Screening and Characterization of Tau Aggregation Inhibitors.
Horsley D, Rickard JE, Vorley T, Leeper MF, Wischik CM, Harrington CR. Horsley D, et al. Methods Mol Biol. 2024;2754:93-104. doi: 10.1007/978-1-0716-3629-9_5. Methods Mol Biol. 2024. PMID: 38512662
Aggregation of tau protein is a pathological hallmark of Alzheimer's disease and other neurodegenerative tauopathies. Inhibition of tau aggregation may provide a method for treatment of these disorders. Methods to identify tau aggregation …
Aggregation of tau protein is a pathological hallmark of Alzheimer's disease and other neurodegenerative tauopathies. Inhibiti …
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.
Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Wischik DJ, Schelter BO, Davis CS, Staff RT, Bracoud L, Shamsi K, Storey JM, Harrington CR, Wischik CM. Gauthier S, et al. Lancet. 2016 Dec 10;388(10062):2873-2884. doi: 10.1016/S0140-6736(16)31275-2. Epub 2016 Nov 16. Lancet. 2016. PMID: 27863809 Free PMC article. Clinical Trial.
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 pre …
BACKGROUND: Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selecti …
Assays for the Screening and Characterization of Tau Aggregation Inhibitors.
Rickard JE, Horsley D, Wischik CM, Harrington CR. Rickard JE, et al. Methods Mol Biol. 2017;1523:129-140. doi: 10.1007/978-1-4939-6598-4_8. Methods Mol Biol. 2017. PMID: 27975248
Aggregation of tau protein is a pathological hallmark of Alzheimer's disease and other neurodegenerative tauopathies. Inhibition of tau aggregation could provide a method for the treatment of these disorders. Methods to identify tau aggregati …
Aggregation of tau protein is a pathological hallmark of Alzheimer's disease and other neurodegenerative tauopathies. Inhibiti …
34 results