• August 17, 2008 at 8:26 pm

    The news has just come out in the last few days about a Phase II clinical trial in the U.K. that had very good success with Alzheimer’s patients. It utilized a medication which is currently approved for other uses–Urolene Blue.

    The researchers called their version “Rember”, which they say is a more purified form. It is also known as methylene blue. It’s past use has been for urinary tract infections and treatment of carbon monoxide poisoning.

    THIS IS THE FIRST MEDICATION TO SHOW PROMISE WITH REDUCING THE TANGLES INSIDE BRAIN CELLS. THOSE CURRENTLY ON THE MARKET WORK ON THE AMYLOID PLAQUES OUTSIDE THE BRAIN CELLS.

    Here’s a link:

    http://www.medpagetoday.com/MeetingCoverage/ICAD/tb/10320

    This med must be pretty safe if it is an FDA approved drug for these other uses, so it bothers me that it will have to trudge its way through a Phase III trial and whatever else is necessary to bring it to market. The earliest it would be available is 2012 according to what I have read.

    So, I’m posing the question to anyone else who is interested, What can we do to hurry this process along? Donate money? Write to the FDA?

    Are there any doctors who wish to comment on the possibility of an off-label use of urolene blue combined with a very careful monitoring of the patients’ blood and urine chemistry, vital signs, etc., if the patient volunteers?

    My wife is currently in a moderate stage, having had it for about 8 years.

    John1943

  • August 20, 2008 at 5:51 pm

    Came across a new article about methylene blue. Will post the link with a partial quote below.

    http://www.sciencedaily.com/releases/2008/08/080818101335.htm

    “A new study conducted by researchers at Children’s Hospital & Research Center Oakland shows that a century-old drug, methylene blue, may be able to slow or even cure Alzheimer’s and Parkinson’s disease…..”

  • October 5, 2008 at 11:26 pm

    Came across an article stating that Rember is being administered in the form of a nasal spray in a British trial. A nasal spray would bypass the blood brain barrier as well a avoid the blue urine issue.

    That link is:

    http://alzheimers-disease.suite101.com/article.cfm/antialzheimers_nasal_spray_showing_promise

    Have not been able to find a confirming link or one listing the British clinical trials. If someone can please post here or pm me.

  • October 6, 2008 at 8:12 pm

    I’m a little confused by these different reports on Methylene Blue (aka Rember).

    1). A trial (in Scotland?) by Tau Pharmaceuticals reported success in reducing the Tau tangles in the brain cell. Three doses were used: 30, 60, and 100 mg three times per day. The 60 mg dose was said to be most effective. The trial had 321 participants.

    http://www.medpagetoday.com/MeetingCoverage/ICAD/tb/10320

    2). A trial in the U.K., again with 321 patients, again by Tau Pharmaceuticals, but with a nasal spray of Methylene Blue also claims good results reducing Tau tangles in the brain cell.

    http://alzheimers-disease.suite101.com/article.cfm/antialzheimers_nasal_spray_showing_promise

    Are these two separate trials or are the details scrambled up??

    3) A trial in Oakland (California?) used miniscule amounts of Methylene Blue, not to reduce Tau tangles, but rather to maintain robust mitochondria in the brain cells.

    http://www.sciencedaily.com/releases/2008/08/080818101335.htm

    Is anyone able to decipher what all this means??

  • October 7, 2008 at 5:02 am

    Could not find a Taurx study or trial offering a nasal spray. I’m believing that the ‘nasal spray’ story was a reporting error. The only way that we will find out for sure is to contact the people at Taurx that are in charge of the studies. Anyone care to volunteer?

    Was able to come up with a total of 2 Taurx studies at the following link

    http://clinicaltrials.gov/ct2/results?spons=%22TauRx+Therapeutics+Ltd%22&spons_ex=Y

    ClinicalTrials.gov Identifier: NCT00515333 was completed. It originally offered enrollment to 323 individuals. The medication (called TRx0014) consisted of varying doses contained in a “hard capsule” as well as a placebo

    ClinicalTrials.gov Identifier: NCT00684944 is open label and ongoing but not recruiting. Enrollment was to be for 111 individuals. The medication (called TRx0014) is in 30 & 60 mg tid gelatin capsules.

  • October 7, 2008 at 5:06 pm

    I registered as a member of Suite101 and sent an email to Daniel, the author of the nasal spray article, asking for comment on the differences between his article and the other one. If he replies, I’ll report back.

  • October 27, 2008 at 5:20 am

    Just learned that the nasal spray shows promise article posted at
    http://alzheimers-disease.suite101.com/article.cfm/antialzheimers_nasal_spray_showing_promise

    is actually a mish-mosh of 2 stories. One about TauRx’s Rember — a portential Alzheimer’s intervention that is not currently being tested as a nasal spray and the other about Allen Pharmaceuticals AL-108–A nasal spray that is being tested as an intervention against mild cognitive impairment.

  • November 3, 2008 at 5:02 am

    Came across an interesting comment to an article about Rember that appeared in Alzforum while attempting to get information about Souvenaid (a breakfast food) being developed by Dannon as an intervention against MCI and very mild Alzheimer’s. The link to the Rember comment which appears toward the middle of the page is:
    http://www.alzforum.org/new/detail.asp?id=1909

    Below is the entire comment (without the list of references) that provides some thoughts as to why Rember might have value:

    Comment by: Jane Karlsson

    Submitted 22 August 2008
    Posted 22 August 2008

    How Does RemberTM Work?
    How exactly does Rember work? We have been puzzling over this in recent days, and are finding it difficult to believe that a drug so remarkably successful (yes, we know the caveats) could act on only one of the many problems in AD brain.

    Rember is methylene blue, we are told. Methylene blue is a redox dye, which means it transports electrons. This is what mitochondria do. Methylene blue has been found to restore cognition to animals with dysfunctional cytochrome oxidase (Callaway et al., 2002), which is of great interest because cytochrome oxidase transports electrons in mitochondria and is low in AD brain (Mutisya et al., 1994).

    Haem synthesis is another potential target of methylene blue. Very recently Atamna et al. (2008) found that methylene blue delays cellular senescence and improves haem synthesis. Haem is made in mitochondria and involves reduction of iron (III) to iron (II) by the electron transport chain, and specifically by cytochrome oxidase (Williams et al., 1976). In fact, cytochrome oxidase is itself a haem […continued] enzyme, which means a defect in haem synthesis could feed back on itself in a vicious circle. Quite possibly the tangles that Rember is targeting would not develop in the first place if mitochondria were working properly to make resources available for breaking down faulty proteins before they become a problem. Rember dissolves tangles in vitro, like some other redox dyes (Wischik et al., 1996). Tau-tau interaction is thought to be the target, but it might not be the only one. According to Yamamoto et al. (2002), tangles isolated from AD brain can be dissolved by reduction of iron (III) to iron (II), which mirrors what methylene blue might be doing in haem synthesis (see above), and in methaemoglobinaemia, where it does indeed reduce iron (III) to iron (II) (Bradberry, 2003). Iron (III) can aggregate hyperphosphorylated tau via the phosphate groups, say Yamamoto et al., but iron (II) cannot. Iron is a problem in AD brain (Smith et al., 1997), and perhaps its ability to aggregate tau is just as important as its promotion of oxidative stress.

    The success of Rember might have even wider significance. Very recently Leslie Klevay published a paper in Medical Hypotheses entitled “Alzheimer’s disease as copper deficiency” (Klevay, 2008). Klevay is best known for the copper deficiency theory of heart disease (Klevay, 2000). Heart disease shares important characteristics with AD, not least high serum homocysteine (Whincup et al., 1999) and low cytochrome oxidase activity (Burke and Poyton, 1998).

    Cytochrome oxidase is a copper enzyme as well as a haem enzyme. Copper is required for other aspects of iron metabolism besides haem synthesis, including iron efflux from the brain (Xu et al., 2004). Homocysteine metabolism, too, is intimately associated with that of copper (Bethin et al., 1995a and 1995b). Methylation reactions are inhibited by S-adenosylhomocysteine (SAH), which is broken down by SAH hydrolase, a copper protein. Another key enzyme in the pathway, methionine synthase, may require copper in addition to vitamin B12 (Tamura et al., 1999). Most significantly, copper and protein methylation are involved in NGF-dependent neurite outgrowth, and so is SAH hydrolase (Birkaya and Aletta, 2005).

    High homocysteine means problems with methylation reactions. And here is the link with tangles in AD brain: methylation is needed for assembly of the phosphatase primarily responsible for dephosphorylating P-tau, PP2A (Vafai and Stock, 2002). Obeid et al. (2007) found correlations in neurological patients between CSF P-tau and homocysteine, SAH and the SAM/SAH ratio, and they suggest the link is through PP2A.

    Copper is low in the modern diet, being largely removed during refining of grains, and Table 1 of the 2006 paper by Morris et al. shows an astonishing correlation between copper intake and cognitive function. It was recently found, most intriguingly, that Aβ peptides 1-40 and 1-42 are members of the Ecto-nox family of copper-dependent redox oscillators (Markert et al., 2004), which suggests they are not just toxic cellular junk.

    Methylene blue is a kind of redox oscillator, too. All kinds of biological processes involve redox oscillations, almost certainly including neurite extension and axonal transport. Tangles are produced when these processes malfunction. Even if Rember doesn’t turn out to work quite as well as it appears, it will still have made a major contribution to AD research.

  • January 28, 2009 at 4:41 pm

    I have heard that urinary tract infections (UTIs) can cause temporary poor mental performance… so I wonder if that was factored into the TauRX study. If a significant number of the women in the study entered it with low-grade UTIs, and then the women who had the methylene blue got their infections cleared up from the drug, this could be the reason for improved mental performance vs. the control group, rather than the drug’s possible effect on Alzheimers.

    If they didn’t check for UTI’s then this was simply a poorly designed study.

    Perhaps someone from TauRx would be willing to comment on this.

    Rich

  • February 1, 2009 at 9:29 pm

    Richz—As a point of interest….Men as well as women get UTI’s.

    My loved attempted to qualify for the BAP trial…During the screening they did a urine sample. He participates in the Dimebon trial…At least one urine sample is obtained during each visit. Since they notified me of a potential health problem during a visit…I’ve got to suspect that they (clinical trial people in general) use all of the information that the blood tests, urine samples, and EKG’s, etc supply.

    In my opinion…The chance that enough people with a UTI that were helped by methylene blue participated in the trial is statistically not worthy of consideration.

  • March 30, 2009 at 10:46 pm

    I have the first signs of Alzheimer’s (and not only one – I have all of the symptoms, and they have been progressively worsening).

    I am heartened by some promising trials and developments, like the atanercept that targets TNF, the various drugs that target beta-amyloid and the PBT2 which “prevents synaptic loss”. That’s all nice and all, but none of these will see the light of day in the next year or two. The good news with methylene blue is that it already exists on the market under the generic name of Urolene Blue.

    Now, here’s the thing: I would like to start self-medicating with Urolene Blue because the side effects seem very small, though having the eyeballs change colour to blue-ish isn’t what I would call a great aid in image. However, my mind is way more important to me than is my looks, and I have to do something to stop my decline.

    So my question is: what do you suggest I do to get Urolene Blue? Note that I live in Europe, and I believe this drug is not present here. If anyone here is from Europe and can prove me wrong, please do and I will be very thankful.

    Oh, and hello all – this is my first post 🙂

  • May 7, 2009 at 8:25 am

    Hi, Methylene Blue is commonly available. However, (and my knowledge here is limited) I understand that almost all available forms (including Urolene Blue) contain metallic impurities, although some contain less than others (for example, some Methylene Blue treatments for fish market themselves as pharma-grade, with lower metallic impurities than other products on the market, although they still contain metallic impurities).

    I couldn’t possibly advise you on whether these impurities would be large enough to cause harm over the long periods you would want to take the drug, although (and please double check this) I believe that the Rember trials used something like Urolene Blue before switching to a more highly purified pharma grade of the drug for Phase II.

    I note that the following France-based company is offering a very pure form of Methylene Blue, with almost no metallic impurities:

    http://www.methylene-blue.com/?gclid=CNqYrM3iqZoCFRK7ZwodIF-82A

    Rgds,