If you use a device running an Android version prior to 7.1.1, beginning January 11 your access from that device to this site and many others will be impaired. For details and solutions, see this topic.

Methylene Blue AD Cure Celebration Thread!

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Methylene Blue AD Cure Celebration Thread!

Postby J11 » Sun Dec 03, 2017 12:03 pm

Phase 2 a.PNG


Welcome to the party! :D

The overwhelmingly positive results from the various Methylene blue/LMTX trials should now be recognized by our forum as essentially a cure or near cure for AD. The figure above from the Taurx website shows that those with mild AD on Methylene blue in the phase 2 trial (with the 138 mg dose) had nearly stable cognitive scores for at least two years. This trial was originally announced at an ICAD meeting almost ten years ago and was recently published. (Notice that the below article on this trial found all sorts of complexities with MB dosing and apparently the correct dosing and how food should be incorporated into the treatment schedule have not been fully resolved.)

This is a very impressive result.

This is not merely a symptomatic treatment.
It would not be unreasonable to call this disease modification.

The result was then replicated (though with caveats) in two follow on phase 3 trials using a chemically similar molecule LMTX.

The second phase 3 trial was recently published in the Journal of Alzheimer Disease (TRx-005 below). The treatment effects and statistical significances were very large. There was a large reduction in brain atrophy for those treated with LMTX monotherapy. For those with APOE 4 the difference was possibly even larger than average. This is not a placebo effect. The p values for many of the measures were <= 0.0001. These were for arms of n < 80. If they had combined the three separate comparisons, the statistical significance level would have been more or less 0.

Let the party begin!

Phase 2 article
jad%2F2015%2F44-2%2FJAD142874.pdf

http://taurx.com/phase-2.html

Phase 3 TRx-005 Mild AD
jad%2F2018%2F61-1%2Fjad-61-1-jad170560%2Fjad-61-jad170560(1).pdf


Phase 3 TRx-015 Mild-Moderate AD
(full free text is at http://taurx.com/phase-3.html for some reason I am unable to upload this file.)

Phase 3 -- TRx-007 bvFTD
Even in this trial which had a top line negative result the treatment group and placebo did better than expected versus historical controls. All the patients received LMTX some at 4 mg bid some at 100 mg bid. Yet, in this trial 80% were not on concurrent AD drugs.
http://taurx.com/trx-237-007-phase-3-cl ... update.pdf
You do not have the required permissions to view the files attached to this post.
Last edited by J11 on Sun Dec 03, 2017 6:30 pm, edited 5 times in total.

User avatar
Julie G
Mod
Mod
Posts: 8615
Joined: Sat Oct 26, 2013 6:36 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby Julie G » Sun Dec 03, 2017 3:28 pm

Here's Alzheimer's News Today's coverage. It's probably a little too soon for a celebration, but a definite "signal" was discerned at the low dose of 4mg b.i.d., which was supposed to serve as the control. Interestingly, when LMTX was combined with traditional AD drugs (cholinesterase inhibitors and/or memantine) no improvement was detected. What do we know about the MOA?

J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby J11 » Sun Dec 03, 2017 4:03 pm

I have thrown in the towel!

The results from the latest phase 3 are simply too good to ignore anymore.
I am not sure whether there exists anything left to debate.
You do not have the required permissions to view the files attached to this post.
Last edited by J11 on Sun Dec 03, 2017 4:16 pm, edited 1 time in total.

J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby J11 » Sun Dec 03, 2017 4:06 pm

All of these Tables demonstrate overwhelming evidence for efficacy.
You do not have the required permissions to view the files attached to this post.
Last edited by J11 on Sun Dec 03, 2017 5:32 pm, edited 2 times in total.

J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby J11 » Sun Dec 03, 2017 4:15 pm

These Tables and Figures are from the second phase 3 trial that has recently been published in JAD.

One of the most striking results is in Table 5. During the first 6 months of LTMX mono-therapy, whole
brain atrophy was statistically equivalent to those using LMTM as add on therapy. Yet, during the 12-18 month
treatment window, a substantial decline in brain atrophication occurred in the mono-therapy but not add on arm
(p-value for mono-therapy of 0.0068).

When you look through the Tables, it is startling how large the treatment effects are and how extremely low
the p-values are. This is even with the use of smallish sample sizes and not combining the results for an
overall result. The p values are in the 0.001 , 0.0001 and lower range. These are not just accounting entries. The
clinical differences that are being reported are substantial. It is not plausible to dismiss a 6 point difference in MMSE
over a 1-2 year treatment horizon. We all know that such a difference is simply massive and would have real world
meaning. (Yet, it is somewhat unclear to me about the MMSE numbers because they appear to jump around a large
amount when changing the different comparison groups.)

Of course, Taurx is now sitting on the extension trial results that treated patients with another 37 months of LMTX
(NCT02245568) after the on trial treatment of 18 months. All of these patients (up to 1000, clinicaltrials.gov has it as still enrolling). Would the benefit of LMTX have lasted for up to 5 years while being treated for AD?


Given the totality of the evidence, an immediate compassionate use / Right to Try program for MB blue
as manufactured by Taurx would seem entirely appropriate.
You do not have the required permissions to view the files attached to this post.
Last edited by J11 on Sun Dec 03, 2017 5:46 pm, edited 1 time in total.

J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby J11 » Sun Dec 03, 2017 5:01 pm

The Figures and Tables from the first Phase 3 are consistent with the recently published results from the second phase 3.
You do not have the required permissions to view the files attached to this post.

J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby J11 » Sun Dec 03, 2017 5:16 pm

I am confused about Supplementary Table 1 versus Supplementary Table 2.

In Supplementary Table 1 those on add-on with 4 mg had a decline of 3.97 points on MMSE versus
3.71 for those on monotherapy 4 mg. A nearly 8 point difference in MMSE is nearly impossible to believe.

Yet, in Supplementary Table 2 the -3.97 change is maintained for the add-on therapy group while for the
LMTM monotherapy 4 mg group it has changed to -0.26. It appears to be the same group of 52 patients,
while the reported value has changed from 3.71 --> -0.26.

However, when looking at the broad outline of the numbers, the two phase 3 studies are showing consistent
and large benefit for the treatments. These are not small patient sub-groups. In some studies where they try
and massage numbers, there might only be a handful of patients involved. The add on LMTM 4 mg group had
close to 300 patients.
You do not have the required permissions to view the files attached to this post.

User avatar
Julie G
Mod
Mod
Posts: 8615
Joined: Sat Oct 26, 2013 6:36 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby Julie G » Fri Dec 08, 2017 9:28 am

Here's a few press releases that outline the mixed reporting on this one :?.

Neurocritic blogspot:
Clinical Trial for Alzheimer’s Disease- Is LMTX ineffective or unprecendented?
http://neurocritic.blogspot.com/2016/07 ... sease.html

Being Patient:
Alzheimer’s Drug Completes Phase 3 Trial With Optimism—But Is It Cause to Celebrate?
https://www.beingpatient.com/taurx-lmtx/

Orangeblossom
Senior Contributor
Senior Contributor
Posts: 802
Joined: Tue Nov 07, 2017 10:11 am

Re: Methylene Blue AD Cure Celebration Thread!

Postby Orangeblossom » Fri Dec 08, 2017 11:18 am

How does it work, please?

I understand it is good to have hope, however it's also good to be critical and analytical too, isn't it. We need to question things before we celebrate too much!

How long term are these studies?
How are the side affects and how long have they looked at for side effects?

Oh, just had a look at the links. That helps give the bigger picture... :?- and the front page of the UK Times article :shock:

J11
Contributor
Contributor
Posts: 1585
Joined: Sat May 17, 2014 4:04 pm

Re: Methylene Blue AD Cure Celebration Thread!

Postby J11 » Fri Dec 08, 2017 3:04 pm

Orangeblossum, the methylene blue/LMTX trial results are difficult to interpret when only looking at the headlines.
There are a few confusing aspects of these trials that have obscured the efficacy signals that were being sent.

The biggest problem was that no phase 1 trials were ever published for methylene blue and no phase 1 or 2 trials were ever published or perhaps even conducted with LMTX. This resulted in tremendously confused clinical trials that had unresolved issues related to pharmacokinetics and other difficulties.

When the LMTX phase 3 results were first reported at ICAD in July 2016, I also had thought they were too compromised to offer a clear indication of the effectiveness of the treatment. However, now that the second phase 3 trial of LMTX has been reported, I have reevaluated my stance. From my understanding as of now, the totality of evidence from the phase 2 MB, 2 phase 3 LMTX in AD and the 1 phase 3 in FTD offer substantial supporting evidence for their effectiveness in Alzheimer's disease. In the phase 2 trial, MB essentially stopped the disease progression over the course of 1 year. No currently available treatment offers anything close to such a treatment effect.

It would probably be best to reserve this thread for the potential celebrations that might occur for LMTX/MB and post the various concerns to the other MB thread. I think that these results are good enough that these two threads should be pinned to the top of the Prevention and Treatment subforum.


Return to “Prevention and Treatment”

Who is online

Users browsing this forum: No registered users and 38 guests