Another Human Study Shows Methylene Blue (MB) May Treat Alzheimer Disease (AD) If Used On Its Own

[haidut]

A few months ago, a thread was posted about the news published by mainstream media that MB "failed" in a human trial for AD. It only failed when it was combined with other drugs currently used for AD, as those drugs are mostly cholinergic and highly excitotxic. When used on its own, MB showed robust benefit.
Methylene Blue Fail Alzhemiers Trial - (No It Didn't)

Now, a follow up study confirmed those results and again showed benefit of MB when used on its own. The hunt it now on for funding to do a large scale clinical trial with only MB. However, there does not seem to be much interest in funding such a trial as MB is dirt cheap and unlike some other more exotic chemicals it cannot be pulled from the market by the FDA (i.e. Google for "pyridoxamine" for more info on that).
Oh well, at least the good news is out for all to see/read

Second phase III study results for anti-tau Alzheimers treatment released – Press Releases
"...“A previous study tested LMTX in a group of people with mild to moderate Alzheimer’s, most of whom were taking existing, approved Alzheimer’s medications. While overall LMTX did not lead to the benefits researchers were hoping to see, the results pointed to potential improvements in a small number of people who took the drug by itself and not in combination with existing Alzheimer’s drugs."

“The results published this week also showed some potential benefits for LMTX as a monotherapy when compared against its effects alongside existing Alzheimer’s drugs, but we can’t draw any firm conclusions without more research. There are a number of reasons people with Alzheimer’s may not take currently approved medications and, while the researchers tried to take these into account, they may explain why the disease appeared to progress more slowly in people who took LMTX as a monotherapy. “In order to get a clearer idea of the effects of LMTX, we now need to see carefully planned studies that focus on LMTX alone, and don’t involve people who are taking other Alzheimer’s medications.”

 

[paymanz]

So lmtx is similar to methylene blue?

 

[haidut]

So lmtx is similar to methylene blue?

It is methylene blue. Google it.

 

[paymanz]

It is methylene blue. Google it.

Googled with no success.

According to your link:

LMTX is a second-generation drug aimed at blocking the build-up of tau protein in Alzheimer’s. The drug, given twice daily as a pill, is based on the structure of a chemical called methylene blue, used as a dye in research and to aid surgery

I dont have knowledge in chemistry,but its Hydromethanesulphonate , it has a hydro,but there is no hydrogen in methylene blue.

 

[haidut]

Googled with no success.

According to your link:


I dont have knowledge in chemistry,but its Hydromethanesulphonate , it has a hydro,but there is no hydrogen in methylene blue.

It is just a slight modification of methylene blue to "improve stability". There is nothing to improve, methylene blue is actually even more stable than this derivative and when I asked the company over email they said they came up with this salt for "legal reasons" and could not provide ANY information on how its stability is better than plain MB. Here is a link showing synonyms for LMTX. One of its other names is leucomethylene blue.
LMTM

Google a bit more about that company and their previous rodent studies. They used plain methyleen blue and when they saw it works came up with this patented compound.

 

[paymanz]

It is just a slight modification of methylene blue to "improve stability". There is nothing to improve, methylene blue is actually even more stable than this derivative and when I asked the company over email they said they came up with this salt for "legal reasons" and could not provide ANY information on how its stability is better than plain MB. Here is a link showing synonyms for LMTX. One of its other names is leucomethylene blue.
LMTM

Google a bit more about that company and their previous rodent studies. They used plain methyleen blue and when they saw it works came up with this patented compound.

Thanks!

 

[Kloppstock]

MB will have no chance of halting AD alone, there are two many-tau-sites that nature have stored for other solutions.

It will just as little as acetylcholinesterase inhibitor will continue to work after 12 months unless you use both of these ability's the correct way

 

[haidut]

MB will have no chance of halting AD alone, there are two many-tau-sites that nature have stored for other solutions.

It will just as little as acetylcholinesterase inhibitor will continue to work after 12 months unless you use both of these ability's the correct way

I disagree, simply because AD is neither tau nor beta-amyloid driven pathology. It is simply brain diabetes, so anything that improves sugar metabolism in the brain will probably work. MB is one such agent, aspirin is another, thyroid is a third, and inhibitors of fatty acid oxidation (or lipolysis) a third, and so on. You know about the (apparently) successful AD human trial with 3g niacinamide daily, right?

 

[jb116]

Even in mainstream science they have first, moved away from amyloid as cause. Secondly, the tau "tangles" sound eerily like lost function -> lost structure.
Deranged metabolism can lead to lost function -> lost structure. "Tangles" sound like lost structure; sounds like a result of deranged metabolism.

 

[johnwester130]

MB will have no chance of halting AD alone, there are two many-tau-sites that nature have stored for other solutions.

It will just as little as acetylcholinesterase inhibitor will continue to work after 12 months unless you use both of these ability's the correct way

obviously a whole body approach is needed.

b1,b2, b3,
aspirin, caffeine.
coconut oil,
progesterone
taurine
lysine
k2
etc

could be used with methylene blue.

 

[Kloppstock]

I disagree, simply because AD is neither tau nor beta-amyloid driven pathology. It is simply brain diabetes, so anything that improves sugar metabolism in the brain will probably work. MB is one such agent, aspirin is another, thyroid is a third, and inhibitors of fatty acid oxidation (or lipolysis) a third, and so on. You know about the (apparently) successful AD human trial with 3g niacinamide daily, right?

What makes you sure that simply brain diabetes is not a result of tau and beta-amyloid driven pathology? i have a model in my head of how this is possible that i hope to get recognized for sooner or later.

Yes i am familiar since i currently use niacinamide as Alzheimer treatment , but not on 3 mg, and you probably know that niacinamide inhibits a specific tau site including microtubule tweaking.
And what does aspirin do?, reverses acetylated tau.
I also wanna add a acetylcholinesterase inhibitor if you wanna improve sugar metabolism and indirectly halt tau from the other direction. Galantamin alongside with MB will be perfect together on correct dose

 

[jb116]

What makes you sure that simply brain diabetes is not a result of tau and beta-amyloid driven pathology? i have a model in my head of how this is possible that i hope to get recognized for sooner or later.

Yes i am familiar since i currently use niacinamide as Alzheimer treatment , but not on 3 mg, and you probably know that niacinamide inhibits a specific tau site including microtubule tweaking.
And what does aspirin do?, reverses acetylated tau.
I also wanna add a acetylcholinesterase inhibitor if you wanna improve sugar metabolism and indirectly halt tau from the other direction. Galantamin alongside with MB will be perfect together on correct dose

And what's driving that pathology: a metabolic disorder.

 

[Kloppstock]

And what's driving that pathology: a metabolic disorder.

And what is a metabolic disorder: Amyloid beta in distant pathway, or its tau who are metabolic and starts in the liver, and amyloid is in the blood brain barrier.
Its already proven that tau is the driver anyhow, i can only inter-connect details, my poor attention often miss the bigger classifications, and its not needed by me to get forward anyway, but by others

 

[jb116]

And what is a metabolic disorder: Amyloid beta in distant pathway, or its tau who are metabolic and starts in the liver, and amyloid is in the blood brain barrier.
Its already proven that tau is the driver anyhow

Well, no, that's not what a metabolic disorder is. That is a byproduct of a metabolic disorder. I think you are overthinking the tenses here. "Diabetes of the brain" is to denote an energy deficit. Energy problems are metabolic disorders. From that arises glycatation for example. We shouldn't blame proteins in that case, but pufas and methylglyoxal... Protein under assault within a metabolic deranged body can lead to these conditions. Stress also leads to the production of possibly harmful substances. Dr. Peat once mentioned microwaves increasing beta amyloid for example. Damaged proteins, tau and amyloid production are not drivers per say, they are more like victims and henchmen respectively. So we don't point to the by-product and say they are the cause but recognize the external factors that interrupt metabolism that otherwise keeps things in working order; keeps function and therefore structure in order.

 

[haidut]

What makes you sure that simply brain diabetes is not a result of tau and beta-amyloid driven pathology?

It has been tested so many times. All drugs that were developed to inhibit tau/beta-amyloid accumulation failed clinical trials. Same with the cholinergic drugs. Acetylcholine is an excitotoxic neurotransmitter so drugs that promote such signalling are likely to worsen AD pathology and would certainly never improve it. It is really not surprising considering that estrogen manifests most of its toxic effects on the brain through the cholinergic system and women have 3-4 higher incidence of AD. Anyways, the beta amyloid, tau and acetylcholine theories have been pretty consistently been falsified over the last 20 years and another tau busting drug just failed in trials this past summer.
Since 2002, 99%+ of Alzheimer Disease trials have failed

Anticholinergic drugs are therapeutic for AD. The adamantane drugs for AD like memantine are fradulently marketed as NMDA antagonists while in reality their main mechanism of action is anticholinergic. The reason they are marketed as NMDA antagonist is that advertising them as anticholinergics will invalidate the theory that acetylcholinesterase inhibitors are beneficial and will kill multibillion dollars in sales. Same case as the drug tianeptine - it acts in a directly opposite way to SSRI drugs and as such will never be approved in most Western countries even though it is a blockbuster antidepressant with rapid onset (1-2 days) and no side serious side effects in therapeutic doses.
I am not saying protein aggregation in the brain is completely benign, but so far it looks a lot more like a symptom than a cause. So far the evidence shows that the "brain diabetes" is driven by estrogen, PUFA and inflammation. It is well-known that inflammation, iron and PUFA perodixation byproducts like MDA trigger protein aggregation (lipofuscin) in many tissues, including the brain. Not many studies have looked at whether the metabolic pathology in brain of AD patients is driven by lipofuscin, but judging from the studies below it is very very likely.
Increased Pufa Oxidation May Be Biomarker For Alzheimers
Blocking PUFA Metabolism May Reverse Alzheimer Disease (AD)
Another Study Links PUFA To Alzheimer Disease (AD)
Dementia Breakthrough - Alzheimer Disease Linked To Endotoxin And Iron

 

[haidut]

Well, no, that's not what a metabolic disorder is. That is a byproduct of a metabolic disorder. I think you are overthinking the tenses here. "Diabetes of the brain" is to denote an energy deficit. Energy problems are metabolic disorders. From that arises glycatation for example. We shouldn't blame proteins in that case, but pufas and methylglyoxal... Protein under assault within a metabolic deranged body can lead to these conditions. Stress also leads to the production of possibly harmful substances. Dr. Peat once mentioned microwaves increasing beta amyloid for example. Damaged proteins, tau and amyloid production are not drivers per say, they are more like victims and henchmen respectively. So we don't point to the by-product and say they are the cause but recognize the external factors that interrupt metabolism that otherwise keeps things in working order; keeps function and therefore structure in order.

This. Exactly.

 

[Kloppstock]

Acetylcholine is an excitotoxic neurotransmitter so drugs that promote such signalling are likely to worsen AD pathology and would certainly never improve it. It is really not surprising considering that estrogen manifests most of its toxic effects on the brain through the cholinergic system and women have 3-4 higher incidence of AD

I totally agree about anticholinergics, and by a coincidence it lowers tau (memantine) that obviously is the other protein you wanna target..

(and you do know that metylenic blue posses ACHEI-powers that target amyloid-beta, why do you think only people who didn't take ACHEI improved, cause the ACHEI-effect got doubled and created an imbalance if they took both, i seem to be the only person on earth realizing that?)

..since you prefer niacinamide, aspirin, methylene blue, no matter if you and Peat have decided this proteins is not the real start of the disease, and i also want you to google "tau missmetabolism" at will, i found it pretty recently myself

I wonder, have there been any studies that confirm this likely excitotoxic effect on ACHEI? my theory is that this occur from and after the day ACHEI stops work, that pretty logic that the creditworthiness becomes depleted, however wish me good luck arguing with a doctor about that, i say its they who shall prove ACHEI is still active by experiencing what happens when you stop.

The doctor will then warn (and therefore say no to the proposition) about a drop in cognition for several weeks ahead!! if you first lower-dose, and if you find that lower dose worse/stop...it will have a hard time to retake the level that you lost (in their imagination) from the high dose that they think must be beneficial...
however just as cognition can temp improve (i think all this failed studies have one thing in common am i right about that? that they start to fail after long-time testing) why should not cognition temp drop just for a while being ACHEI-dose immune

 

[d1d2]

We shouldn't blame proteins in that case, but pufas and methylglyoxal...

Is methyglyoxal not a beneficial substance per Koch, Travis, etc?

 

[haidut]

I totally agree about anticholinergics, and by a coincidence it lowers tau (memantine) that obviously is the other protein you wanna target..

(and you do know that metylenic blue posses ACHEI-powers that target amyloid-beta, why do you think only people who didn't take ACHEI improved, cause the ACHEI-effect got doubled and created an imbalance if they took both, i seem to be the only person on earth realizing that?)

..since you prefer niacinamide, aspirin, methylene blue, no matter if you and Peat have decided this proteins is not the real start of the disease, and i also want you to google "tau missmetabolism" at will, i found it pretty recently myself

I wonder, have there been any studies that confirm this likely excitotoxic effect on ACHEI? my theory is that this occur from and after the day ACHEI stops work, that pretty logic that the creditworthiness becomes depleted, however wish me good luck arguing with a doctor about that, i say its they who shall prove ACHEI is still active by experiencing what happens when you stop.

The doctor will then warn (and therefore say no to the proposition) about a drop in cognition for several weeks ahead!! if you first lower-dose, and if you find that lower dose worse/stop...it will have a hard time to retake the level that you lost (in their imagination) from the high dose that they think must be beneficial...
however just as cognition can temp improve (i think all this failed studies have one thing in common am i right about that? that they start to fail after long-time testing) why should not cognition temp drop just for a while being ACHEI-dose immune

My opinion is that both tau and b-amyloid accumulation are just signs/symptoms of local metabolism derangement, not a cause of pathology by themselves. Most mainstream AD researchers agree that misfolded proteins are a mostly a biomarker of impaired cellular turnover more than anything else. Even a single night of poor sleep can produce these misfolded proteins in very high, without causing any dementia symptoms. Catching up on sleep or increasing glucose intake clears those proteins away.
Just 1 night of bad sleep boosts amyloid beta in brain - Futurity

 

[Kloppstock]

My opinion is that both tau and b-amyloid accumulation are just signs/symptoms of local metabolism derangement, not a cause of pathology by themselves. Most mainstream AD researchers agree that misfolded proteins are a mostly a biomarker of impaired cellular turnover more than anything else. Even a single night of poor sleep can produce these misfolded proteins in very high, without causing any dementia symptoms. Catching up on sleep or increasing glucose intake clears those proteins away.
Just 1 night of bad sleep boosts amyloid beta in brain - Futurity

AD-patients cant catch up though cause A-beta and tau are misfolded in AD only, and i think you have the answer there who promotes that A-beta doesn't clean on catchup.

Most mainstream researchers rather agree that its either amyloid or tau, and only a handful of them suggest you need to target soluble a-beta and soluble Tau oligomers together.

They though think AD-patients can compensate for having alot of amyloid and tangles, so researchers looking for stuff that "rescue memory deficits" caused by inflammation for example, so i think these other new pathways/new genes they keep finding are another symptom relief(slow down).
And that's why they think natural herbs for example..achieve best result since they both target inflammation etc(symptoms) while inhibiting proteins so they self-clean in hierarchy.
We all agree its a multi-factorial disease though

impaired cellular turnover

what does turnover mean to you in general, i only knoe what it really means inside AD

And i still want one more answer, the exitototoxism from ACEHI, from where did you get that news?