The study supports an earlier publication reporting that hydromethylthionine mesylate (HMTM) halted progression of neurodegeneration in Alzheimer’s disease (AD) and that participants with Mild Cognitive Impairment (MCI) who received HMTM 16 mg/day experienced statistically significant cognitive improvement over 18 months. Participants also displayed no evidence of statistically significant cognitive or functional decline over a period of two years.
The newly-reported study compared closely matched external placebo data to show statistically significant treatment effects. The external placebo data were necessary because the control arm for HMTM in the original clinical trial (protocol TRx-237-039) used to maintain blinding with respect to slight urinary colouration by HMTM had some activity and so was not a true placebo.
The latest study compared data from participants who received HMTM 16 mg/day in the original trial with data from matched placebo controls from the FDA-sponsored Critical Path for AD (CPAD) database meeting key inclusion/exclusion criteria (protocol TRx-237-080) as well as with other control populations.
The new paper, titled Assessment of clinical and neuroimaging efficacy of treatment targeting tau pathology in mild cognitive impairment and mild to moderate Alzheimer’s disease with hydromethylthionine mesylate using external control data1, reports statistically significant differences relative to three different external control populations. Key analyses suggest that unmeasured confounding is highly unlikely to explain the observed results.
Prof Bjoern Schelter, TauRx’s Chief Analytics Officer, who is lead author of the newly-published paper, said: “The latest results strongly support the effectiveness of HMTM in people living with MCI and mild to moderate dementia due to AD."
“By comparing participants receiving HMTM 16 mg/day with external control populations, we have been able to navigate the blinding problem and so demonstrate consistent and clinically meaningful differences in cognitive decline (ADAS-Cog13) and rate of loss of brain volume at 78 and 104 weeks, as well as a global measure of progression of dementia (CDR-SB) over 104 weeks."
“The latest results are consistent with our earlier report demonstrating that HMTM could have significant treatment effects on neurodegeneration, tau pathology and brain atrophy. The totality of the evidence now available reinforces our belief that HMTM has the potential to offer an accessible oral treatment option which could be delivered safely and with minimal patient/physician burden.”
The original TRx-237-039 (LUCIDITY) trial confirmed HMTM has a benign safety profile 2,3, with headache (1.5%) and diarrhoea (1.2%) reported as the most frequent adverse effects at the 16 mg/day dose.
HMTM is an investigational drug and a Marketing Authorisation Application from TauRx Therapeutics Management Ltd is currently being evaluated by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).
ENDS
About TauRx Therapeutics Management Ltd
TauRx Therapeutics Management Ltd. is the UK subsidiary of TauRx Pharmaceuticals Ltd. TauRx was established in 2002 with a mission to discover, develop and commercialise innovative products for the diagnosis, treatment and cure of neurodegenerative diseases caused through protein aggregation. For more information, visit taurx.com
Media contact
Andy Groundwater // Head of Communications, TauRx // andy.groundwater@taurx.com
About TRx-237-039 (LUCIDITY)
Completed in June 2023, TRx-237-039 was a double-blind randomised controlled Phase 3 global clinical trial comparing change over 12 months in cognitive, functional and brain atrophy outcomes at HMTM doses of 16 mg/day, 8 mg/day and methylthioninium chloride (MTC) at a dose of 4 mg twice weekly as a control in a 4:1:4 randomisation, with a subsequent 12 month open-label extension phase in which all participants received HMTM 16 mg/day. MTC 8 mg/week was used in the control group to maintain study blinding for slight urinary colouration, which can be a known harmless side effect of the drug. Measurements of ADAS-Cog13, ADCS-ADL23, and whole brain volume MRI were taken over 24 months and compared to baseline.
Tau pathology in Alzheimer’s
Through dedicated research programmes, it is understood that certain age-related factors lead to misfolding and aggregation of tau protein, and the subsequent formation of tau tangles in Alzheimer’s. Pathological aggregation of tau protein disrupts and damages neuronal function. The process begins many years before symptoms of dementia are seen. Tau pathology has been proven to correlate with the clinical decline (loss of cognitive function and ability to care for oneself) commonly seen in people with Alzheimer’s, establishing it as an important target for treatment. HMTM is primarily a tau aggregation inhibitor, which effectively crosses the blood brain barrier to target the source of this damaging process. HMTM and MTC both have a secondary pharmacological action which is symptomatic through increasing acetylcholine levels in parts of the brain essential for memory functions.
About Alzheimer’s disease
The hallmark neuropathological features of Alzheimer’s disease are amyloid and tau pathology 4
Dementia and Alzheimer’s disease have been a leading cause of death in the UK for over a decade, accounting for 12.6% of all deaths registered 5,6
76,894 people in the UK died from dementia in 2024 – more than other major conditions such as heart disease and stroke 7
Alzheimer’s disease imposes a large economic burden on the NHS and wider health system, with annual healthcare combined health and social care costs reaching nearly £29,000 per person year, driven largely by hospital admissions and care home needs 8
Alzheimer’s disease is characterised by progressive cognitive decline, including impairments in memory, executive function, attention, language, and visuospatial processing. Patients with Alzheimer’s disease also present with neuropsychiatric symptoms, such as social withdrawal, impulsivity, depression and mood disturbances 9
Patients with Alzheimer’s disease may have significantly reduced quality of life compared with healthy individuals, due to progressive impairment of social engagement and functional abilities 10
Alzheimer’s disease has a very large impact on family members and carers, often affecting their emotional wellbeing, sleep, relationships, and personal time 11
NfL (neurofilament light chain) and pTau217 (tau phosphorylated at amino acid position 217) are blood biomarkers which measure neurodegeneration and tau pathology
Current diagnostic criteria emphasise biomarker testing as sufficient for diagnosis, including amyloid PET, CSF Aβ42/40, plasma p-tau181/Aβ42, and p-tau217. Full dementia evaluations may incorporate these alongside other tests to assess disease severity, rule out alternative causes for cognitive impairment, and guide staging and treatment decisions 12
Current standard clinical management offers temporary symptomatic relief, with no disease-modifying therapies available through the NHS
References
Schelter et al. The Journal of Prevention of Alzheimer’s Disease, 2026
Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease (ClinicalTrials.gov ID NCT01689246)
Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild Alzheimer's Disease (ClinicalTrials.gov ID NCT01689233)
Office for National Statistics – Leading causes of death, UK
Alzheimer’s Research UK: Dementia is still UK’s biggest killer – where do we go from here?
Porsteinsson et al. J Prev Alzheimers Dis. 2021;8(3):371-386
Shah et al. Alzheimer Disease & Associated Disorders, 2024;38(4):338–343
