What do you think about Rember, the new drug in phase II, presented at ICAD 2008?
for information you can visit:
http://en.wikipedia.org/wiki/Rember
http://www.taurx.com/
It seems to stop the progression of Alzheimer and other Taupaties, thanks to the action of Methylthioninium Chloride (Methylene Blue) that solves the tau protein aggregates.
waiting for you considerations.
Luke

Hi Luke,
Rember looks very promising, along with Dimebon, Gammagard and others. Unfortunately, they are all 1 1/2 - 2 years away from FDA approval and their availability to the public.

Recently came across 2 postings of the same Rember article on the internet. It said that the people in the Britain clinical trial (I think Phase III) were taking Rember via an intranasal spray. This would be encouraging for 2 reasons:

1. I think that the nasal pathways may be more effective and may allow Rember to reach the brain and perhaps cross the blood brain barrier

2. Using this method would probably eliminate the 'blue urine' quandry.

Have been unable to locate a listing of clinical trials held outside of the US to confirm this. CAN ANYONE FIND ONE? If so, please, POST A LINK. It would be helpful.
--------------------------------------------------------------------
Luke there is another Rember thread in existence. It is called "Big breakthrough in Alzheimers Drug". You might want to look at it for additional sources of information. To keep information about the topic in one place I may transfer some of my information here on a time permitting basis...and...Would certainly not object if someone copied mine or theirs into this thread.

Our Neurologist was at the presentation in Chicago and his opinion was not very good with all the data they presented. It left a lot to be desired, unfortunately

[quote]Britain[/quote]
Skericheri,

I am not able to find any on-line information of Rember being given nasally. Do you have a link?
My impression has been that there was only one clinical trial, done in the UK, with 3 different oral doses.

Thanks,
John1943

Thanks,
John 1943

You can find informations about clinical trials of Rember searching for TRX0014 on clinical trials.gov web site:
http://clinicaltrials.gov/ct2/results?term=trx0014

Luke

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.

There is a good Rember article at:

http://news.bbc.co.uk/2/hi/health/7525115.stm

Rember, too, looks to be very promising -- however, did you see it's tentative release date? 2012! Ahhhhhhhhh

We start two weeks ago a treatment for my mother, who suffers of Primary Progressive Aphasia, with Methylthioninium Chloride (Methylene Blue), 60 mg three times per day. I'll keep you informed about the results.
Luke

Thanks for the info, Luke.

How is the dose given--as a hard pill, a capsule, or a gelcap. Just curious.

[quote]Primary Progressive Aphasia,[/quote]
Hi Luke. I thought of another question. I can find no reference to Methylene Blue being an approved treatment for PPA. Were you able to get a doctor to write an "off label" prescription? I sure would like to ask him to write one for Alzheimer's.

Hi John,
the dose is given by capsule. Methylene Blue, as you said, is not an approved treatment for PPA, but we asked our family doctor for an off label treatment, and he prescribe a recipe that a pharmacist has prepared. It's not difficult, but i hope that will also be a valid treatment for the pathology of my mother.
Luke

Luke---Please tell me more and post follow-ups

--------------------------------
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.

Hey Luke, My mother also has PPA and I was wondering how is your mother responding to the off label treatment?

Luke, could you tell us more about the "recipe" that the pharmacist prepares?

I tried getting my mother's physician to prescribe some form of MB "off label", but she wouldn't budge. She said that using MB for AD or any other tauopathy is not the "standard of care for our area". What a bunch of bull. I guess the "standard of care" is to let people wither away.

I really hate doing it, but in desperation we've had to resort to using MB from a tropical fish store. Kordon's is the brand. I mean, it's made for fish, not people. I think it should be OK if there is nothing else in it but MB. It never hurt my fish when I used it for treating "ich". We don't use much. About 8 drops per gallon of liquid, given in 1/2 cup portions, 2 times per day. Mostly to prevent neuronal senescence, as the article cited above mentions. We use cinnamon and lithium orotate to target the tau proteins directly, and curcumin in the hopes of targeting amyloid beta (it works for mice). I think this concoction helps, but I would rather use a pharmaceutical grade of MB.

Somebody please check these calculations:

Methylene Blue for "ich" usually comes as a 2.3% solution in water.

One cc, of water weighs one gram. So, one cc of "ich" solution contains .023 grams or 23 milligrams. In order to get to a 60mg dose, you need 60/23 = 2.6 cc of the methylene blue solution from the ich container-- for each dose.

If you buy a pack of standard size, 1cc insulin syringes from the drugstore, it would take 26 units of methylene blue solution, which would be 2.6 "syringefulls".

That sounds like a good bit more than 8 drops per gallon given at a rate of one cup per day.

Of course, the big question is, "Is it safe?"

Are my numbers right?

By the way I propose the insulin syringe as a way to measure. I don't say to inject it.

Your numbers would be correct if I were using a 60mg dose. I would like to, but we are not. Rather, we are pursuing the "very low concentration – about the equivalent of a few raindrops in four Olympic-sized swimming pools of water" approach, as described in the following story. I take it that MB has a hard time crossing the blood-brain barrier, so I'm hoping that one drop for every two cups of liquid, taken 1 cup per day will result in this order of concentration.

"Potential Alzheimer's, Parkinson's Cure Found In Century-old Drug"
ScienceDaily (Aug. 18, 2008)
"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. Used at a very low concentration – about the equivalent of a few raindrops in four Olympic-sized swimming pools of water – the drug slows cellular aging and enhances mitochondrial function, potentially allowing those with the diseases to live longer, healthier lives..."
http://www.sciencedaily.com/releases/2008/08/080818101335.htm

Is it safe? I don't know. If I could get one of these troglodyte physicians around here to write a script for a prescription MB, I assure you, I would use it.

Hi,
My mother is getting the treatment from one month so is too soon to say something. The recipe i asked to prepare is made only of Methylthioninium Chloride (Methylene Blue) 60 mg, in capsule (not liquid!!!). Our doctor made the prescription and the pharmacist did the galenic preparation, i don't know in the USA if there are difficulties, not in Italy, cause the principle is commercialized for treatment of other illnesses. But you must be carefel because there could be negative interaction (also fatal) with other drugs such as SRI (Serotonin Reuptake Inhibitors), so it's always better and recommended to ask the doctor and to be followed by him if you decide for this off-label treatment.
Hope to be usefull
Luke

Luke,

Thank you for your comments.
Please keep us informed of your mother's progress.

Does she also take Aricept, Exelon, Razadyne, or Namenda?

There is a medication in the U.S. called Urolene Blue. It is a solid made with Methylene Blue. However, doctors will not prescribe it for Alzheimer's because it is not approved by the FDA for that use.

hi Luke --
It has been two months since your last post...
How is your mom doing?

My mom also has Alzheimers and she is on Aricept now.
Rich

Hi Rich
my mom continues to take methylene blue, she seems quite stable, but i think is to soon to say if it works, certainly for my mother doesn't seem to make miracles ... but i must also say that she doesn't suffer from AD but PPA (Primary Progressive Aphasia). Anyway I'll post any changes.
Luke

Luke,

I ran across the web site of a methylene blue producer called "ProVepharm". They claim to sell methylene blue that is made by a "Heavy-metal-free process". The link is:

http://www.methylene-blue.com/info.php

That statement about heavy metals has me worried about the safety of other formulations. Possibly this is why Dr. Wischick stated that the formulation used in his clinical trial was more highly purified.

Would your pharmacist have any knowledge of whether heavy metal contamination is a genuine concern with this product?

The target of Rember and methylene blue is corrupted tau protein aggregations, if I understand the reports correctly.

But recently we have learned about niacinamide (nicotinamide) and this may have the same effect (at 2000mg spread throughout the day???). By all means, pursue Rember and methylene blue, but while we wait for physicians to decide that it does not violate the "standard of care" to prescribe MB, (I tried... couldn't get the PCP to budge), we can try niacinamide and cinnamon to combat the tau problem.

There must be sources for methylene blue as an "industrial chemical", because a 2.3% solution is readily available in tropical fish stores. But, considering the "heavy metal contamination" issue, I would only pursue this in desperation. I wonder if this stuff would be relatively easy to make in a home lab? I mean, criminals make all these illegal drugs in makeshift labs, why not something helpful like MB?

Hi John,
i don't know about heavy metal contamination in MB, in the recipe there's no mention about this, and i don't know if in the fabrication process can be occur contamination of heavy metal as you say. Anyway my mother doesn't present any collateral effects, so i think there's not the problem you say in what she takes. The problem is that i don't yet know if this medication is a valide treatment or not
Luke

OK,

I'll start the posting of Rember/Urolene Blue/Methylene Blue by copying and pasting Bob Lee's post here:

"Star Pharmaceuticals is the owner of the brand Urolene Blue. It is out of production. I received an email from them this week stating that they may resume by the end of the summer.
The French company that makes ProveBlue sent me an email yesterday stating:
"Following recent announcements in the general and scientific press concerning new uses for Methylene Blue, we have received numerous requests from around the world for samples of Proveblue® Methylene Blue and drug products that contain it.

Provepharm is a manufacturer of the drug substance (also known as Active Pharmaceutical Ingredient – API). In order to comply with ethical, insurance and regulatory standards, unfortunately, we can only supply drug substance and drug products :

to registered pharmaceutical companies such as wholesalers, distributors, finishers etc.
or for use in official clinical trials subject to IND or CTA approval or equivalent
or to registered pharmacists via an approved wholesaler or distributor, in compliance with local law, for use in pharmacy compounding (extemporaneous preparations)
We cannot supply drug products for off-label, unapproved uses or uses subject to patent protection by third parties."
So that avenue is blocked.
Based on the MD "act" who posts here and is treating her Mom, it appears that garden variety methylene blue shows an effect.
If you do not have a doctor who is willing to be more aggressive in approaching the treatment of a fatal disease than a referral to Hospice, find a new one.


Buckle your seatbelt!"

Thank you John.

I have also found a neurologist who is willing to prescribe the drug. So would like to find out more from folks who have had some experience with this medication.

I would still like to see a spec sheet from a pharmacy that lists what the impurities are in Methlene Blue.

Urolene Blue was a medication that likely was used for short periods of time--to cure urinary tract infections and carbon monoxide poisoning. Any impurities would not have a chance to accumulate in the body. Using it for years requires a greater degree of diligence.

Also, we should consider that the claim made for Rember is that it slows the rate of decline. It is not a magic bullet.

There are plenty of supplements that we have discussed--cinnamon, curcumin, nicotinamide, alpha GPC, resveratrol. It is said that these also slow the rate of decline.

How does one measure a slower rate of decline?

I tried giving my wife methylene blue for about two months--65 mg, 3 times a day. Nothing miraculous happened. When I learned about the potential for heavy metal contamination, I bailed out.

John...this medication, MB, was used for years. So there is long history in its use for UTIs. I need to do more research to answer the heavy metal question and your concerns.

Your point is well taken re all of the known drugs and alternative medications. We are all grasping at straws. There is no known cure as there is no known cause of AD. So we all do whatever we can to slow down the progression. In my opinion, different things appear to work, as possibly in the future, they will discover that there are different diseases that are currently under the umbrella of AD diagnosis.

In the few months you have used MB did you see any changes in your LO's behavior or personality? Thanks for sharing.

Believe me, SCS, if I had noted any sort of good response I would have let everyone know about it. All I can say is that nothing bad happened.

Luke

My wife also has Primary Progressive Aphasia. Have you ever seen this web page. I have the full text of the study. It looks promising. I wonder if anyone else has tried prednisone.

www.ncbi.nlm.nih.gov/pubmed/19001174

Bob ... prednisone treatment would only be effective if the PPA were caused by an autoimmune disorder. Having had a vasectomy may be a risk factor for men to develop an autoimmune-based PPA. The man described in the case report had had a vasectomy, so they gave prednisone treatment a shot.

You might want to ask your wife's doctors if they have tested her for a possible autoimmune disorder. Many doctors are not aware that these can cause a treatable dementia.

John;

Am concerned that you may have used a preparation of methylene blue (MTB) that was not prepared for oral use. Would agree that you should be concerned about purity. Do you have an old fashion pharmacy near you? There are pharmacies that specialize in mixing compounds ordered doctors. They would be able to make a safe oral MTB compound similar to that used in Rember study. MTB should be fairly simple to get prescription for as it has a long history without any harmful outcomes. Trick is getting a pharmacist to fill it while waiting for it to come to market.

Neurologist who is very upbeat about Rember says that does not work 100% for everyone. What else is new?????? Good luck.

SCS,

I used laboratory grade powder dissolved in distilled water. Replaced fish oil in gelcaps with the solution by syringe

Going to see a new neurologist this spring. Maybe he will prescribe what other did not.

However, I do believed that the French company that mentioned heavy metals was discussing pharma grade.

For those whose doctors will supply a prescription, here is a licensed pharmacist experienced in compounding medical grade chemicals and delivering them for treatment nationwide.

http://www.pvpsc.com/sec/1

Linda's prescription will be ready Friday.
They are packaging the mb in small capsules to make it easier for her to take.
If anyone is going the alternate route on sourcing non-medical mb, consider talking to your doctor and arranging a prescription for a medical grade solution from a licensed pharmacist.

I have no real need for this section, but have been casually keeping up. I wonder if it would be helpful for one of you to ask the Adm. to re-name this thread "Rember/Methylene blue"?? I had no idea they were connected. Of course, I hadn't investigated, either . it would also help, if someone was doing a specific search for the threads titled methylene blue.

Have copied this link by John1943...great site. Thank you John.

http://www.adcs.org/

Good luck, Bob. Don't foget to warn Linda that she should expect some blue stains on her undergarments. That stuff is very, very blue.

JAB

PPA patients are normally tested for everythng under the sun and then told that they have PPA and that there is no known cause or treatment. That is why some of us search the internet for possible breakthroughs and participate in discussion groups like this. Prednisone worked for one patient. My question is whether anyone else has tried it for PPA. I know that this is a Rember discussion group, but I don't hear any evidence of great success in using Rember for PPA patients.

Bob---I can't answer your question. Charlie seems to have 'garden variety' A/D. I remember seeing the word Prednisone mentioned on the Progressive Supranuclear Palsy forum located at: http://forum.psp.org/ but do not remember the context. You might want to check out the site and do a search on Prednisone.

Bob, I'm sure this has been horribly frustrating for you, trying to find a way to help your wife.

Prednisone is prescription only, and since it is a very effective immunosuppressant, the very high doses that are needed to treat an encephalopathy are not willingly prescribed by a doctor without a very good reason. In fact, there is a dear lady on the EOAD forum who is a doctor herself; she has an autoimmune encephalopathy, and she knows high doses of corticosteroids could help, but her dementia can't be treated due to other health issues which would be exacerbated by the corticosteroids.

Many doctors are unaware that autoimmune disorders can cause a treatable dementia.

If your wife has been tested for an autoimmune disorder and the results were negative, then prednisone won't help.

If she hasn't been tested, you might want to suggest it to her doctors. Or contact the Neuro Department at Mayo Clinic, either in Scottsdale AZ or Rochester MN. They have quite a bit of experience in diagnosing / treating autoimmune dementias. Dr Richard Caselli (Scottsdale) has published quite a bit in this area.

JAB

We went through a full line of testing at the Mayo Clinic. She was tested for everything. PPA is not considered by them and almost everyone else as an autioimmunne disease. All they offered was speech therapy, which is a joke. However, in the study I sited above two respected neurologists concluded that PPA might just be a treatable autioimmune disease and that in one case they found that prednisone worked. When the Mayo Clinic offers no treatment we are left to try out the "might just be" possibilities. PPA is so rare that few want to do studies on it because there aren't any big bucks to be made if they found a medicene that works.

I'm finding papers from back in the 1990's that talk about the possibility that there might sometimes be an autoimmune component to some FTD disorders, so this concept isn't anything new. I've been looking into FTD for a friend, and it's a very complex group of dementias, and the knowledge about the underlying pathologies are constantly changing.

You might think about contacting the doctors who wrote that paper, and see what they think about trying the prednisone for your wife.

I now have the methylene blue capsules for Linda.
Pawtuxet Valley Pharmacy will be stocking it for Linda and others, by prescription.

http://www.pvpsc.com/

I drove over to RI to pick up the first prescription to save time, but will have them mail the refills from now on for convenience.
We were charged $50 for (90) 60mg capsules, a months supply at 3 per day.

The facility is well maintained and professional and the staff was helpful.
A good resource.

Hi Bob, how MB effect on Linda? I know it is too soon to ask, but I really have a question about MB. According to Wikipedia's descreption, "the formulation used was different from that commonly available as a medicine and caution has been expressed about use of methylene blue as a treatment for Alzheimer's", so what is that?

H.J.
No change in Linda yet at day 3.
Any differences in the mb used for Rember is a good question.
It seems logical that a common medication to be reintroduced as a new treatment would need to be blessed by secret fairies and oh so different from the common stuff.
But this is now and Rember is not for sale anywhere. Since mb is pretty benign, what the hell nothing ventured nothing gained is a strategy. Especially since doing nothing will prove fatal anyway. For anyone approaching severe AD, Treatment available in a couple of years is given posthumously.

"It seems logical that a common medication to be reintroduced as a new treatment would need to be blessed by secret fairies". Bob, you have very sensitive sense about it, and I feel the same way too. Like enbrel, it is really effective for someones, not for all, though it is very convincing. I will still cosider it for my mom.
Keep trying, no experiment no advance. We all keep a hope of being "blessed by secret fairies".

Bob...have not read the Rember study...how long did it take to note changes?

The problem with the Enbrel Fairy Tale is that we were led to believe something should work within 10 minutes! That alone kept the serious researchers from believing....the effect was probably due to more oxygen in the brain from being tilted upside down...(my humble opinion).

Most drugs that are being trialed mainly work from keeping folks from getting worse. Nothing to my knowledge has reversed the disease to any great extent. We just need to keep Linda walking! I would think 3 days is not enough time to seriously judge any drug therapy.

Bob, I totally know where you're coming from and I can relate to your frustration. I too have heard of success with treating PPA as an autoimmune disorder and my advice to you is, if you can have your wife cleared for any medical conditions that would contradict with using Prednisone, then find a doctor who is willing to give it a go, and try it, you have nothing to loose.

Also, I wouldn't be discouraged by the 'theory' that if your wife has been tested for 'known' autoimmune disorders and she is all clear, then an autoimmune disorder cannot be causing her PPA. First of all, the reports of success noted with PPA in a person who had a vasectomy done some years prior, as I'm sure you're aware, did not make reference to 'any' diagnosable autoimmune disorder and I repeat these individuals didn't have 'any' diagnosable autoimmune disorder. There was simply a postulate put forward that an 'autoimmune' mediated pathology could be at fault causing the patients symptoms. This gained favour with the treating doctor after it was brought to his attention that there was a high incidence of vasectomy and PPA. Hence, in this instance, vasectomy was identified as a causal factor, and just like vasectomy as a potential cause of PPA remained relatively unknown until late (Mayo Clinic are not even aware), the same could be assumed for any number of 'unknown' autoimmune processes taking place that could cause PPA. Not long ago 'vasectomy' was one of those unknown processes. So rather than say, oh what can we test for and what can't we test for, please give Prednisone a go, nothing to loose!

I don't deny that some autoimmune diseases that can cause dementia exist and can be tested for, however, it is clear that not all that cause dementia can. So the only thing you can do is try it out and use this as an example to rule out autoimmune processes. No different to how Prednisone was trialled for Alzheimer's, the researchers didn't ask themselves do these test subjects have an autoimmune illness, that was irrelevant; they simply treated for an autoimmune process with the hope there would be some success.

So just try it, nothing to loose.

There is a link between vasectomy and PPA? Wow. Do you have a link to a web site, report, or news article for more information on this?