Rember
Encyclopedia
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 trial
s 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 .
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.
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.
Debate began soon after the announcement over the funding of the drug under the UK's National Health Service
.
The initial press release from TauRx has been characterized as "very aggressively worded". A lengthy article at the Alzheimer Research Forum
provoked further comments.
to potassium cyanide
poisoning and as a test for gastric secretion. For other uses, see Methylthioninium chloride#Medicine.
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
, or methylene blue, proposed trade name Rember) is an investigational drug being developed by the University of Aberdeen
University of Aberdeen
The University of Aberdeen, an ancient university founded in 1495, in Aberdeen, Scotland, is a British university. It is the third oldest university in Scotland, and the fifth oldest in the United Kingdom and wider English-speaking world...
and TauRx Therapeutics
TauRx Therapeutics
TauRx Therapeutics Ltd is a startup pharmaceutical company that is based in Singapore.The company was founded in 2002 by the late gynecologist, surgeon and venture capitalist K. M...
that has been shown in early clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s to be an inhibitor of Tau protein
Tau protein
Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes...
aggregation. The drug is of potential interest for the treatment of patients with Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. Its development appears to be related to claim 7 of .
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
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
studies suggest that methylene blue might be an effective remedy for both Alzheimer's and Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
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 AberdeenUniversity of Aberdeen
The University of Aberdeen, an ancient university founded in 1495, in Aberdeen, Scotland, is a British university. It is the third oldest university in Scotland, and the fifth oldest in the United Kingdom and wider English-speaking world...
held a Phase IIB clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
on 321 people with mild Alzheimer's disease in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
and Singapore
Singapore
Singapore , officially the Republic of Singapore, is a Southeast Asian city-state off the southern tip of the Malay Peninsula, north of the equator. An island country made up of 63 islands, it is separated from Malaysia by the Straits of Johor to its north and from Indonesia's Riau Islands by the...
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
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
. 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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
; as methylene blue also has effects on the synuclein
Synuclein
Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors.- Family members :The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein...
fibres in the brain.
If the results of the two trials correlate, the drug could be on the market by 2012.
Debate began soon after the announcement over the funding of the drug under the UK's National Health Service
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
.
The initial press release from TauRx has been characterized as "very aggressively worded". A lengthy article at the Alzheimer Research Forum
Alzheimer Research Forum
Alzheimer Research Forum , or Alzforum as it is known among Alzheimer’s researchers, is a website which exploits to the fullest the potential of web technology to accelerate research into Alzheimer's disease...
provoked further comments.
Other uses
Methylthioninium chloride is approved as an antidoteAntidote
An antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek αντιδιδοναι antididonai, "given against"....
to potassium cyanide
Potassium cyanide
Potassium cyanide is an inorganic compound with the formula KCN. This colorless crystalline compound, similar in appearance to sugar, is highly soluble in water. Most KCN is used in gold mining, organic synthesis, and electroplating. Smaller applications include jewelry for chemical gilding and...
poisoning and as a test for gastric secretion. For other uses, see Methylthioninium chloride#Medicine.
See also
- Progressive supranuclear palsyProgressive supranuclear palsyProgressive supranuclear palsy is a degenerative disease involving the gradual deterioration and death of specific areas of the brain....