Handfuls of pills are not needed

The pharmaceutical company TauRx reported unexpected results of pharmacokinetic analysis of the relationship between the dose of treatment, blood concentration and pharmacological activity of the drug hydromethylthionine in relation to the brain of more than 1,000 patients with mild to moderate Alzheimer's disease. These results proved that even at the lowest dose of hydromethylthionine previously tested in two global Phase 3 clinical trials (8 mg/day), the drug suspended cognitive decline and brain atrophy.

Hydromethylthionine in tablet form is approved by the World Health Organization with the nonproprietary name LMTM. This drug blocks abnormal aggregation of tau protein in the brain, leading to the progression of clinical dementia. During 2012-2016, 1,700 patients with mild to moderate Alzheimer's disease participated in phase 3 of global clinical trials. Hydromethylthionine was tested at doses of 150-250 mg/day in the experimental group and at a much lower dose (8 mg/day) in the control group – just to change the color of urine, which can sometimes accompany treatment. Unexpectedly, there was no difference in any of the clinical results between the groups of high and low doses of hydromethylthionine.

To study the results in depth, the researchers conducted a pharmacokinetic population analysis using plasma concentration data from 1,162 patients who participated in either of the two completed phase 3 studies to measure how the concentration of the drug in the blood is related to its effect on the brain. The researchers found that when taking hydromethylthionine at a dose of 8 mg / day in most patients, the level of the drug in the blood was high enough to cause a significant effect on maintaining cognitive functions and reducing brain atrophy. They concluded that a slightly higher dose of hydromethylthionine, equal to 16 mg / day, would achieve the concentration in the blood necessary to achieve maximum activity of the drug. Higher doses do not make sense, since they do not lead to an increase in the effectiveness of treatment. The so-called pharmacological plateau explains why the effects of hydromethylthionine in high doses were no better than in patients from the group of hydromethylthionine 8 mg/day.

Discussing the effectiveness of hydromethylthionine at a dosage of 8 mg/day, the authors cite the following data: on the ADAS-cog scale, the effect was about 7.5 points, or three times more than with drugs commonly used for the treatment of Alzheimer's disease, and would be equivalent to an 85% reduction in cognitive impairment over 65 weeks.

The ADAS-Cog assessment of Alzheimer's disease is a standard technique used to measure neuropsychological changes in clinical studies of Alzheimer's disease. A change of 4 points is usually considered an indicator of a clinically significant difference.

The analysis also showed that in patients taking hydromethylthionine as an adjunct therapy to the commonly used symptomatic treatments for Alzheimer's disease, the maximum effect was half as much. This observation confirms the hypothesis that symptomatic medications for Alzheimer's disease reduce the therapeutic effects of hydromethylthionine.

Hydromethylthionine is taken in a convenient oral form at home and does not require patients to visit clinics for intravenous infusions or injections, unlike various other treatments for Alzheimer's disease that are currently undergoing clinical trials. If the planned studies of the effectiveness of the drug at a dose of 16 mg/day are completed as successfully, hydromethylthionine can be attributed to disease-modifying therapy, since it acts on the aggregation process of tau protein.

Article by B.O.Schelter et al. Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer's Disease is published in the Journal of Alzheimer's Disease.