Journal of Prevention of Alzheimer’s Disease publishes trial results showing HMTM potentially offers accessible oral treatment option for patients with early Alzheimer’s disease

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Date: 26-January-2026

Journal of Prevention of Alzheimer’s Disease publishes trial results showing HMTM potentially offers accessible oral treatment option for patients with early Alzheimer’s disease

TauRx Therapeutics Management Ltd today announced results from its Phase III LUCIDITY trial evaluating the efficacy and safety of hydromethylthionine mesylate (HMTM) in the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) have been published in The Journal of Prevention of Alzheimer's Disease.

The trial reports that participants with MCI who received HMTM 16 mg/day experienced statistically significant cognitive improvement over 18 months, with no significant cognitive or functional decline observed over a period of two years.

Professor Claude Wischik, TauRx Co-Founder and Chairman, who is lead author of the paper, said: “These results show HMTM has the potential to offer an accessible oral treatment option with a benign safety profile which could be delivered with minimal patient or physician burden. 

“The study also found starting HMTM treatment early in the disease process is important for preservation of cognitive function and that it impacts the underlying disease process in AD. 

“This study confirms results from earlier trials showing that HMTM has a benign safety profile, with headache (1.5%) and diarrhoea (1.2%) reported as the most frequent adverse effects.” 

The trial evaluated the safety and efficacy of HMTM in 598 participants with MCI and mild to moderate dementia due to Alzheimer’s disease. All participants were amyloid β-PET positive, with 44% (263) meeting the clinical criteria for MCI due to AD, and 56% (335) diagnosed with mild to moderate dementia due to AD. 

The paper, entitled 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 disease¹, reports on the trial which was conducted at 82 sites across Canada, the European Union, United Kingdom, and United States.

It compared 16 mg/day and 8 mg/day doses of HMTM with 4 mg twice weekly doses of methylthioninium chloride (MTC). MTC was required as a urinary colourant to preserve blinding due to possible urinary discolouration caused by HMTM. 

In the trial, HMTM and MTC were compared on cognitive and functional endpoints for the first 52 weeks followed by all patients receiving HMTM 16 mg/day to 104 weeks in a modified delayed-start trial design. Unexpected initial symptomatic activity in the MTC arm interfered with the intended primary outcome analyses at 52 weeks, but not with longer-term outcomes in participants with MCI. 

MCI participants receiving HMTM 16 mg/day showed statistically significant differences in cognitive decline (ADAS-cog₁₃) at 78 weeks and 104 weeks in analyses specified prior to the 104-week database lock. Those starting HMTM 16 mg/day after a 52-week delay could not catch up with those starting earlier due to ongoing neurodegeneration during the first 52 weeks in those receiving MTC. 

The benefit of HMTM 16 mg/day has been confirmed in a further study utilising closely matched external placebo arm cases from a well-documented trial database to provide true placebo controls not confounded by the blinding problem.

In the early start MCI group receiving HMTM 16 mg/day, statistically significant cognitive improvement over baseline score was sustained for 78 weeks, with no significant cognitive or functional decline over 104 weeks. There was a significant reduction in progression of neurodegeneration measured by NfL change in blood at 52 weeks in both the whole and MCI populations. This was consistent with significant reductions in progression of brain atrophy in scans at 52 and 104 weeks, and a reduction in progression of tau pathology (measured by pTau217 change in blood) in MCI. 

The study confirms the results from earlier trials showing that 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 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. The company’s headquarters are in Aberdeen and its primary research facilities and operations are based at the University of Aberdeen. For more information, visit taurx.com

Media contact

Andy Groundwater // Head of Communications, TauRx // andy.groundwater@taurx.com

About LUCIDITY

Completed in June 2023, LUCIDITY was a double-blind randomised controlled Phase 3 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

• 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^4,5
• 76,894 people in the UK died from dementia in 2024 – more than other major conditions such as heart disease and stroke⁶
• Alzheimer’s disease imposes a large economic burden on the NHS and wider health system, with annual healthcare costs averaging £4,548 per person and combined health and social care costs reaching nearly £29,000 per person year, driven largely by hospital admissions and care home needs⁷
• 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 neuropsychiatric symptoms, such as social withdrawal, impulsivity, depression and mood disturbances⁸
• Patients with Alzheimer’s disease have significantly reduced quality of life compared with healthy individuals, due to progressive impairment of social engagement and functional abilities⁹
• Alzheimer’s disease has a very large negative impact on family members and carers, often affecting their emotional wellbeing, sleep, relationships, and personal time¹⁰
• The hallmark neuropathological features of Alzheimer’s disease are amyloid and tau pathology¹¹
• 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 decisions¹²
• Current standard clinical management offers temporary symptomatic relief, with no disease-modifying therapies available through the NHS

References

1. Wischik et al. The Journal of Prevention of Alzheimer’s Disease, 2026
2. Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease (ClinicalTrials.gov ID NCT01689246)
3. Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild Alzheimer's Disease (ClinicalTrials.gov ID NCT01689233)
4. Office for National Statistics – Leading causes of death, UK
5. WHO data – United Kingdom
6. Alzheimer’s Research UK: Dementia is still UK’s biggest killer – where do we go from here?
7. Edwards et al. Aging and Health Research, 2024;4(1):100180
8. Porsteinsson et al. J Prev Alzheimers Dis. 2021;8(3):371-386
9. Martyr et al. Psychol Med. 2018;48(13)(suppl):2130–2139
10. Shah et al. Alzheimer Disease & Associated Disorders, 2024;38(4):338–343
11. Thal et al. Molecular Neurodegeneration, 2025;20:33
12. Jack et al. Alz & Dementia, 2024;20:5143–5169