- |||||||||| rivastigmine / Generic mfg.
Preclinical, Journal: Neuroprotection of Cholinergic Neurons with a Tau Aggregation Inhibitor and Rivastigmine in an Alzheimer's-like Tauopathy Mouse Model. (Pubmed Central) - Apr 16, 2024 This phenotype is reversible by HMTM, but at the same time appears to be subject to a homeostatic regulation induced by chronic pre-treatment with an acetylcholinesterase inhibitor, which interferes with the efficacy of HMTM. The strongest phenotypic reversal coincided with a normalization of the tau load in the cortex and hippocampus of L1, suggesting that tau accumulation underpins the loss of cholinergic markers in the basal forebrain and its projection targets.
- |||||||||| memantine / Generic mfg., LMTX (hydromethylthionine) / TauRx, rivastigmine / Generic mfg.
Preclinical, Journal: Mitochondrial Effects of Hydromethylthionine, Rivastigmine and Memantine in Tau-Transgenic Mice. (Pubmed Central) - Jul 18, 2023 In summary, traditional anti-dementia drugs impair mitochondrial function while HMT has no adverse effects on mitochondrial respiration in tau-transgenic mice. These results support the further development of HMT as an anti-dementia drug.
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Causal association of cardiovascular risk factors with Alzheimer (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_3933; Data suggest not only a reduced cognitive efficacy of HMT in subjects pre-exposed to the choline esterase inhibitor rivastigmine, but also offer mechanistic explanations for potential interactions at presynaptic function and for transmitter release. Baseline brain FDG-PET images of participants with a diagnosis of AD from two large clinical trials of hydromethylthionine were classified into
- |||||||||| LMTX (hydromethylthionine) / TauRx
Clinical, P3 data, Clinical Trial,Phase III, Journal: 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. (Pubmed Central) - Oct 26, 2022 If the primary end points are met, the data will provide confirmatory evidence of the clinical and biomarker benefits of hydromethylthionine mesylate in minimal to moderate AD. As low-dose oral hydromethylthionine mesylate is simple to use clinically, does not cause amyloid-related imaging abnormalities and has a benign safety profile, it would likely improve AD management.
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HMTM Topline Results of Phase 3 LUCIDITY – The First Tau Aggregation Inhibitor (Grand Ballroom AB - Tower 2) - Oct 5, 2022 - Abstract #CTAD2022CTAD_240; P3 Hydromethylthionine mesylate (HMTM) 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)...This presentation will consider the extent of the potential transformation of the patient pathway that HMTM could provide. All abstracts are embargoed until the day and time of presentation at the CTAD Conference S14
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Journal: Effects of Moderate Altitude Training Combined with Moderate or High-altitude Residence. (Pubmed Central) - Aug 5, 2022 On the other hand, LHTM augmented minute ventilation (76±14 to 88±10 l·min;p=0.04) and systemic blood oxygen saturation by 2±1%; (p=0.02) with no such differences observed following the LMTM. Collectively, despite minor physiological differences observed between the two tested altitude training modalities both induced comparable exercise performance modulation.
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Journal: Hydromethylthionine enhancement of central cholinergic signalling is blocked by rivastigmine and memantine. (Pubmed Central) - Feb 12, 2022 Our findings establish that the drug interaction that was first observed clinically has a neuropharmacological basis and is not restricted to animals with tau aggregation pathology. Given the importance of the cholinergic system for memory function, the potential for commonly used AD drugs to interfere with the treatment effects of disease-modifying drugs needs to be taken into account in the design of clinical trials.
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Journal: Fungally Derived Isoquinoline Demonstrates Inducer-Specific Tau Aggregation Inhibition. (Pubmed Central) - Nov 21, 2021 When compared to a tau aggregation inhibitor currently in clinical trials (LMTX, LMTM, or TRx0237), ANTC-15 and LMTX were found to have opposing inducer-specific activities against ARA and heparin in vitro-induced tau filaments. These findings may help explain the disappointing results in translating potent preclinical inhibitor candidates to successful clinical treatments.
- |||||||||| memantine / Generic mfg.
Preclinical, Journal: Mechanisms of Anticholinesterase Interference with Tau Aggregation Inhibitor Activity in a Tau-Transgenic Mouse Model. (Pubmed Central) - May 25, 2021 Since the interference is dictated by homeostatic responses to prior symptomatic treatment, it is likely that there would be similar interference with other drugs tested as add-on to the existing symptomatic treatment, regardless of the intended therapeutic target or mode of action. The present findings outline key results that now provide a working model to explain interference by symptomatic treatment.
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Journal, IO Biomarker: Disease-modifying therapies for tauopathies: agents in the pipeline. (Pubmed Central) - Aug 12, 2020 Unfortunately, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. Further evidence will come from ongoing Phase I/II trials on novel drugs and immunotherapeutics with various targets - prevention of deposition or removal of tau aggregates, inhibition of tau phosphorylation/acetylation, modulation of O-GlcNAcylation, activation of autophagy or ubiquitin-proteasome system pathways, and rescue of selected tau loss of function or suppression of tau gene expression.
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Journal: Formaldehyde, Epigenetics and Alzheimer's disease. (Pubmed Central) - Feb 20, 2020 Whereas the safety and efficacy of most tau-targeting drugs have not yet been completely assessed, the first tau aggregation inhibitor, LMTX, failed in a late-stage trial, leading to further recognition of the complexities of AD and reconsideration of the amyloid hypothesis and perhaps the tau hypothesis as well...This review will briefly summarize current knowledge on mechanistic insights into AD, focusing on epigenetic alterations and FA involvement in AD development. The exploration of chemical exposures as contributing factors to AD may provide new inights into AD mechanisms and could identify potential novel therapeutic targets.
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Phase classification, Trial completion date, Trial primary completion date, Monotherapy: LUCIDITY: Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment (clinicaltrials.gov) - Nov 19, 2019 P3, N=450, Active, not recruiting, Inhibitors of the MAPK signal transduction pathway showed significant inhibitory effects on E. multilocularis, suggesting these may be potential candidates for the treatment of alveolar echinococcosis. Phase classification: P2/3 --> P3 | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Dec 2021
- |||||||||| A review of volumetric MRI changes in AD treatment trials and a framework for their interpretation () - Oct 16, 2019 - Abstract #CTAD2019CTAD_48;
Discordant findings were small in magnitude and more likely associated with lower doses or shorter follow-up times. Interrogating atrophy in a larger set of brain regions, and examining the patterns of relative and absolute treatmentplacebo differences across brain regions, may help further interpret volumetric changes in intervention trials.
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