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Alzheimer's Disease

TauRx Goes Into Phase III For Alzheimer’s

I can’t even count the number of e-mails I’ve gotten over the last few years asking about TauRx and their Alzheimer’s program, which made a big splash back in 2008. Finally, there’s some news to report. The company is starting Phase III clinical trials, and has announced new financing to see these through. The company is based in Singapore, and they’re getting money from a large multinational company in the region.
Good for them. The tau-based therapy they’re working on is a very interesting idea, and (of course) extremely significant if it actually works. I’m happy to see that it’s going to get a real chance to prove itself, and I look forward to seeing the results. Their earlier compound (“Rember”) was reformulated methylene blue, but they now seem to have an improved version to go ahead with (and not just in Alzheimer’s, apparently).
I know I’ll get more mail about this, but let me save time by telling those interested to go here, to a site run by TauRx about their clinical trials. It seems that they have started enrolling patients in North America.

19 comments on “TauRx Goes Into Phase III For Alzheimer’s”

  1. barry says:

    any company trying to deliberately build/buy an archive of “diverse small molecules” will find the occasional dyestuff hitting in a high-throughput assay. My experience has been that they all flunk Shoichet’s “aggregator test” so far. Maybe this one’s different? But I’d check that result three times.

  2. ablueman says:

    This has to be the only trial where the placebo group are on API (8mg/day). I’ll let you work it out ….

  3. luysii says:

    #2 What’s API (Aricept?)

  4. Anonymous says:

    Active Pharmaceutical Ingredient

  5. anon says:

    luysii I’m guessing its Active Pharmaceutical Ingrediant. Methylene blue has the side effect of making your urine turn green/blue and therefore a placebo has to do the same thing – so it has to be low dose methylene blue. I hope they have the doses right and don’t see a massive “placebo” effect.
    Isn’t leuco just colourless i.e. reduced methylene blue. In which case its starting to look like some of the chlorpromazine type anti-depressants. Is it working through the reduced form with an effect on transmission or through the oxidised form as a tau detangler.
    I’d hate to be running the bioanalytics on this – how do you stop the forms interconverting on the lc ?

  6. luysii says:

    It is worth keeping in mind that methylene blue is a Nissl stain. Neurons (particularly long projection neurons to the spinal cord, and from the spinal cord to muscle) have huge cellular volumes. Although there is some protein synthesis from ribosomes in dendrites, most is carried out in the cell body which has to make the proteins for a huge cytoplasmic space (often 100 or more times larger than the visible cell body). This leads to huge amounts and clumps of ribosomes, visible in the light microscopy as Nissl substance. Nissl developed these stains a century ago, long before we even knew what a ribosome, RNA or DNA was. Nissl stains, such as methylene blue are positively charged and bind to the negatively charged phosphates linking the ribonucleotides together in RNA.
    Something to keep in mind when you think of methylene blue or something like it having an effect on proteins. Methylene blue also inhibits guanyl cyclase, important in nitric oxide synthesis.
    Hopefully the trial will work. We certainly need something better than what we have.

  7. Lane Simonian says:

    Methylene blue also inhibits inducible nitric oxide synthase. Inducible nitric oxide combines with superoxide anions to form peroxynitrites. Peroxynitrites contributes to the hyperphosphorylation of tau proteins and mediates the nitration of those proteins so they cannot be reconstituted for proper neurotransmission (incidentally peroxynitrites nitrate amyloid plaques increasing their aggregation).
    FASEB J. 2006 Jul;20(9):1431-42.
    Peroxynitrite induces Alzheimer-like tau modifications and accumulation in rat brain and its underlying mechanisms.
    Zhang YJ, Xu YF, Liu YH, Yin J, Li HL, Wang Q, Wang JZ.
    SourcePathophysiology Department, Key Laboratory of Neurological Disease of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
    Abstract
    To investigate the upstream effector that led to tau hyperphosphorylation, nitration, and accumulation as seen in Alzheimer’s disease brain, and the underlying mechanisms, we bilaterally injected SIN-1, a recognized peroxynitrite donor, into the hippocampus of rat brain. We observed that the level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h after drug administration, and these alterations were prevented by preinjection of uric acid, a natural scavenger of peroxynitrite.
    Find the right peroxynitrite scavenger or scavengers and you not only slow the progression of Alzheimer’s disease, you partially reverse it. What a happy note just before Thanksgiving!

  8. Anonymous says:

    Wischik came up with Methylene Blue in 1994 or so and has since been pursuing it doggedly. He has not published any of his findings in peer reviewed journals, and many in the field think that he is off the mark (he appears to think the same about his peers). It would be very interesting to actually see the Phase II data.
    In a field where no breakthroughs have been made in a decade, hope dies last.

  9. That’s awesome. I can’t wait to see the results of this!

  10. That’s awesome. I can’t wait to see the results of this!

  11. Anonymous says:

    four 11C labels in one molecule?
    a 1:1 molar ratio of 18F?
    that rubbish made my day…

  12. Ricky Connolly says:

    ^ What he said.

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