Surprising findings by researchers in a new study by TauRx show that the drug hydro-methyl thionine is capable of producing noticeable effects on brain atrophy and cognitive decline even at the lowest dose.
The World Health Organization (WHO) approved this drug for blocking tau protein in the brain. Many medical experts consider tau protein as a major contributor to Alzheimer’s disease and dementia.
TauRx researchers tested the drug, which was previously known as LMTM, on over 1,000 Alzheimer’s patients with mild to moderate cases. They found that the lowest dose of the compound, as used in previous research, was able to produce effects on cognitive decline and brain atrophy. This finding came about after studying the relationship between drug doses, levels in the blood, and pharmacological activity.
The surprising findings from this pharmacokinetic analysis first appeared in an online edition of the Journal of Alzheimer’s Disease.
Lower doses good enough
Researchers studied the effects of hydro-methyl thionine on nearly 1,700 patients with mild to moderate Alzheimer’s in Phase 3 global clinical trials. The investigations took place between 2012 and 2016.
Subjects received 150mg to 250mg doses of the drug daily during the trials. As a control for urine discoloration, a possible side effect, researchers also tested a low 8mg daily dose on the subjects. They were surprised to find that higher doses did not make the compound more effective in patients. Clinical results of the Phase 3 trials failed to show any significant difference between the high and low doses.
The 8mg daily dose was the lowest used in two Phase 3 global clinical trials carried out previously on the drug.
Researchers proceeded to use the plasma concentration data of 1,162 patients to perform further pharmacokinetic analysis. These subjects were involved in either of the previous two trials. The research team assessed the relationship between the drug’s amounts in the blood and its brain effects in the patients.
Results showed that most of the participants in the separate analysis had sufficiently high blood levels from the lowest dose. These patients experienced sizeable decreases in both cognitive decline and brain atrophy at the dose.
The researchers opined that a dose of 16 mg a day is enough to get the maximum benefits hydro-methyl thionine has to offer. Higher doses and plasma concentrations do not produce better effects.
Other drugs reduce effects
Alzheimer’s patients typically take certain symptomatic drugs. Often, they also use hydro-methyl thionine to supplement other medications.
Researchers, however, found in this study that the symptomatic drugs can make this compound to be less effective. Its maximum effect reduced by half in patients who were also on symptomatic treatments.
The finding was in line with a hypothesis by the researchers that symptomatic drugs used for Alzheimer’s inhibit the effects of hydro-methyl thionine on the disorder. Phase 3 trial results for the drug led to that hypothesis.
TauRx now plans to move on with a clinical trial to prove that the 16mg daily dose is best.
“Since we already have a substantial database supporting the safety and tolerability of hydro-methyl thionine in clinical trials of patients with mild-to-moderate Alzheimer’s disease, the additional results of this analysis have given us the confidence to expand the scope of the new TauRx Lucidity clinical trial to confirm the potential efficacy of the hydro-methyl thionine 16mg/day dose in these types of patients,” said Prof. Claude Wischik, executive chairman of TauRx Therapeutics Ltd.
A major appeal of the drug is that it comes in tablet form, to be taken by mouth. This will likely make it more appealing to most patients. Some other treatments for Alzheimer’s that are currently going through clinical trials may involve clinic visits to get.