LMTX (hydromethylthionine) / TauRx 
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 23 Diseases   1 Trial   1 Trial   89 News 


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  • ||||||||||  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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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
    Trial completion, Monotherapy:  LUCIDITY: Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment (clinicaltrials.gov) -  May 24, 2023   
    P3,  N=598, Completed, 
    These results demonstrate that the orally administered tau aggregation-inhibitor, HMTM, is able to produce a significant dose-dependent reduction in neurodegeneration in AD as measured by change in plasma NfL levels. Active, not recruiting --> Completed
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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.
  • ||||||||||  rivastigmine / Generic mfg.
    Preclinical, Journal:  HMTM-Mediated Enhancement of Brain Bioenergetics in a Mouse Tauopathy Model Is Blocked by Chronic Administration of Rivastigmine. (Pubmed Central) -  Apr 24, 2022   
    In this study, the changes in l-lactate appear to be regulated by LDH-A, since neither of the experimental conditions affected the levels of LDH-B. The data show that HMTM monotherapy facilitates the use of substrates for energy production, particularly l-lactate, which is provided by astrocytes, additionally demonstrating that a chronic pre-treatment with rivastigmine prevented most of the HMTM-associated effects.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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) -  Sep 23, 2021   
    P3,  N=598, Active, not recruiting, 
    These findings may help explain the disappointing results in translating potent preclinical inhibitor candidates to successful clinical treatments. Trial completion date: Jun 2023 --> Mar 2023 | Trial primary completion date: Jun 2022 --> Mar 2022
  • ||||||||||  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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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 2, 2020   
    P3,  N=500, Recruiting, 
    Typically, this comes from astrocytes, contributing to reversal of spatial learning deficits in L1 mice by enhancing mitochondrial function. Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Dec 2021 --> Jun 2022
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    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.
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    Enrollment change, 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) -  Sep 7, 2018   
    P2/3,  N=375, Recruiting, 
    Trial completion date: Jun 2020 --> Dec 2020 | Trial primary completion date: Jun 2020 --> Dec 2020 N=180 --> 375 | Trial completion date: Feb 2019 --> Jun 2020 | Trial primary completion date: Feb 2019 --> Jun 2020
  • ||||||||||  LMTX (hydromethylthionine) / TauRx
    Enrollment closed, Trial primary completion date:  Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild Alzheimer's Disease (clinicaltrials.gov) -  Jan 9, 2015   
    P3,  N=700, Active, not recruiting, 
    Recruiting --> Active, not recruiting | N=180 --> 220 Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2015 --> Apr 2016