|Systematic (IUPAC) name|
|Mol. mass||319.85 g/mol|
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Methylthioninium chloride (INN, or methylene blue, proposed trade name Rember) is an investigational drug being developed by the University of Aberdeen and TauRx Therapeutics that has been shown in early clinical trials to be an inhibitor of Tau protein aggregation. The drug is of potential interest for the treatment of patients with Alzheimer's disease. Its development appears to be related to claim 7 of US 6953794 Inhibition of Tau-Tau Association. TauRx Therapeutics has suggested that the mechanism by which methylene blue might delay or reverse neurodegeneration in Alzheimer's disease is as an inhibitor of Tau protein aggregation. While methylene blue arguably has an effect on Tau aggregation, it also has an effect on mitochondrial function which is likely to play an important role. In vitro studies suggest that methylene blue might be an effective remedy for both Alzheimer's and Parkinson's disease by enhancing key mitochondrial biochemical pathways. It can disinhibit and increase complex IV, whose inhibition correlates with Alzheimer's disease. 
2008 clinical trial results
The University of Aberdeen held a Phase IIB clinical trial on 321 people with mild Alzheimer's disease in the United Kingdom and Singapore and found that taking the drug 3 times a day over a period of 50 weeks slows down the development of Alzheimer's disease by about 81%.
The patients were split into four groups: one group taking a dose of 30 mg, another taking a dose of 60 mg, a third taking a dose of 100 mg and the fourth taking a placebo. The 60 mg dosage gave the best results, giving an 81% reduction in mental degression compared to those on the placebo. Only those on the placebo experienced a decline in mental function.
A larger Phase 3 trial is planned for 2009 with an idea to see whether methylene blue can prevent the formation of the disease in the first place. TauRx are also looking into starting a trial of the drug on patients suffering from Parkinson's disease; as methylene blue also has effects on the synuclein fibres in the brain.
If the results of the two trials correlate, the drug could be on the market by 2012.
Phase III trial
The form of the prodrug used in the Phase III clinical trial (NCT01689233) has been changed to TRx0237 (tradename LMTX), which is said to be better tolerated and more conducive to maintaining blinding in the trial. A smaller amount of the same prodrug is given to control subjects as a blinding agent.
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