Trial reportJournal of Alzheimer's disease : JAD2020
Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia.
Trial report in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- 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.The journal of prevention of Alzheimer's disease · 2026Trial
- Pathological Disulfide Bond Crosslinking: Molecular Insights into Amyloidogenesis and Diseases Progression.Chembiochem : a European journal of chemical biology · 2025Review
- Twenty years of therapeutic development in tauopathy mouse models: a scoping review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Hydromethylthionine sustains truncated tau-dependent inflammation-lowering effects in mouse brain.The FEBS journal · 2025Article
- Recent Advances in Drug Development for Alzheimer's Disease: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Targeting Tau Protein with Proximity Inducing Modulators: A New Frontier to Combat Tauopathies.ACS pharmacology & translational science · 2025Review
- Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy.Protein & cell · 2025Review
- Article
- The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- The therapeutic landscape of tauopathies: challenges and prospects.Alzheimer's research & therapy · 2023Review
- Lactate: A Theranostic Biomarker for Metabolic Psychiatry?Antioxidants (Basel, Switzerland) · 2023Review
- New Approaches to the Treatment of Frontotemporal Dementia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Human Tau Aggregates Are Permissive to Protein Synthesis-Dependent Memory inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Tauopathies: new perspectives and challenges.Molecular neurodegeneration · 2022Review
- Article
- Pharmacotherapy for Frontotemporal Dementia.CNS drugs · 2021Review
- Tau Oligomers Neurotoxicity.Life (Basel, Switzerland) · 2021Review
- Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.Brain communications · 2021Article
- Long-Term Hydromethylthionine Treatment Is Associated with Delayed Clinical Onset and Slowing of Cerebral Atrophy in a Pre-Symptomatic P301S MAPT Mutation Carrier.Journal of Alzheimer's disease : JAD · 2021Article
- Pharmacophore Modeling and 3D-QSAR Study of Indole and Isatin Derivatives as Antiamyloidogenic Agents Targeting Alzheimer's Disease.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHydromethylthionine is a potent inhibitor of pathological aggregation of tau and TDP-43 proteins.
objectiveTo compare hydromethylthionine treatment effects at two doses and to determine how drug exposure is related to treatment response in bvFTD.
methodsWe undertook a 52-week Phase III study in 220 bvFTD patients randomized to compare hydromethylthionine at 200 mg/day and 8 mg/day (intended as a control). The principal outcomes were change on the Addenbrookes Cognitive Examination - Revised (ACE-R), the Functional Activities Questionnaire (FAQ), and whole brain volume. Secondary outcomes included Modified Clinical Global Impression of Change (Modified-CGIC). A population pharmacokinetic exposure-response analysis was undertaken in 175 of the patients with available blood samples and outcome data using a discriminatory plasma assay for the parent drug.
resultsThere were no significant differences between the two doses as randomized. There were steep concentration-response relationships for plasma levels in the range 0.3-0.6 ng/ml at the 8 mg/day dose on clinical and MRI outcomes. There were significant exposure-dependent differences at 8 mg/day for FAQ, Modified-CGIC, and whole brain atrophy comparing patients with plasma levels greater than 0.346 ng/ml with having minimal drug exposure. The exposure-response is biphasic with worse outcomes at the high concentrations produced by 200 mg/day.
conclusionsHydromethylthionine has a similar concentration-response profile for effects on clinical decline and brain atrophy at the 8 mg/day dose in bvFTD as recently reported in AD. Treatment responses in bvFTD are predicted to be maximal at doses in the range 20-60 mg/day. A confirmatory placebo-controlled trial is now planned.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.