1229 replies to this topic

[mag1]

Did Methylene Blue truly fail?

Primary readout was negative, though a prespecified subgroup not taking AD drugs was positive.

 

 

 

http://www.multivu.c...-1617511063.pdf

 

 

 

 

The taurx website is calling it a success.

http://taurx.com/press-releases/

 

Those who were not taking other AD drugs had clear benefit.

 

"The ADAS-cog decline analysis produced highly statistically significant treatment effects of -6.3 +/-1.4 (p<.0001) and -5.8 +/-1.4 (p<.0001)

units after taking 75mg b.i.d or 125mg b.i.d of LMTX® as monotherapy respectively, while the ADCS-ADL decline analysis produced a

statistically significant treatment effect of 6.5 +/-1.8 (p=.0013) and 6.9 +/-1.9 (p=.0007) following treatment of 75mg b.i.d or 125mg b.i.d of

LMTX® as monotherapy respectively."

 

6.9 points benefit on ADCS-ADL is large.

For Alzheimer families this is a practical measure of day to day functioning that should indicate the true burdens associated with dementia care.

If these results can be clarified, then LMTX looks like it could be a game changer in Alzheimer's treatment.

http://www.dementia-...s-adl_scale.pdf

 

 

 

 

Is this party hat time?

Edited by mag1, 27 July 2016 - 01:49 PM.

[Logic]

Not sure about that helper phage but I am attempting to isolate the m13 from sewer water. I am still in the process of collecting needed supplies. The refrigerated centrifuge seems to be the only equipment needed and I have just received that from ebay and of course it doesnt work as advertised but I have identified the issue and have parts on order to repair. Hopefully I will be making the first attempt in 2 or 3 weeks.

 

One thing to consider is if enough of the phage can travel up the nose to do any good. Maybe if its snorted every day for a long period of time.

 

 

My hat is of to you mrwhitee!

I have not gone into how the phage is isolated/purified from all the other pathogens in the drain water?

[mag1]

People! People! Please!

 

Methylene Blue is looking like it is the one.

They stopped NEARLY COMPLETELY STOPPED progression of AD in mild to moderate patients over the 15 month treatment interval.

[Might not be as popular as logic, though when the dam breaks ole mag1 will capitalize, underline, highlight in neon red and if I could

surround in purple polka dots. Mag1 goes the extra mile for the people!]

 

(Difference in ADCS-ADL decline was almost 7 points. This is the typical change over the course of a year. So over the 15 months

we would have been looking at 8.75 point change expected. LMTX is preventing 7 of 8.75 points of the decline. Not bad!) 

 

This is large news.

Still somewhat clear about how small the subgroup of monotherapy patients was, though even so this is BIG.

 

Comments please!

 

Could someone get a delegate at the ICAD conference in Toronto to turn their cell phone on at the presentation today between 4:15 - 5:45 PM?

The whole world is watching!

The people have a right to know!

Edited by mag1, 27 July 2016 - 03:45 PM.

[mag1]

It would be so great if there were some sort of a stock market proxy for this result.

When Biogen reported good Alzheimer's results, their market capitalization was reflecting their AD assets as being worth $100 billion.

 

Sure would be nice to know whether the market valuation of taurx's AD pipeline is now worth $100 billion +?

Edited by mag1, 27 July 2016 - 04:54 PM.

[resveratrol_guy]

Methylene blue sounds exciting, but we've been dabbling with it for years around this forum, and the results are unimpressive at best. Perhaps it helps a narrow cohort, such as folks with mild Alzheimer's who are not taking pharmaceutical drugs. Of course, maybe if we take it everyday for years, it will prevent dementia, but that would be very difficult for us to determine in a useful timeframe.

 

I still give you points for trying. What we need is a 3BP of dementia, which would be M13 (thanks, Logic) but for its challenges as a practical treatment.

Edited by resveratrol_guy, 28 July 2016 - 01:16 AM.

[mag1]

res, thank you for replying!

 

Where are the people on this one?

The results seem hugely huge.

 

The phase 2 trial had this strange requirement that people could not be on standard of care.

Seems a little odd, standard of care should be a minimum,though if everyone had been on standard of care in this trial the monotherapy result would not have been shown.

 

Anyway they got a positive result in that trial.

They prespecified the no other treatment (monotherapy LMTX treatment arm) in these phase 3 trials.

 

The result in that subgroup have been startling. They halted about 80% of the expected progression on ADCS-ADL.

Almost the exact same result in the phase 2.

 

The p values were SMALL! p=.0013 in one treatment arm and p=0.0007 in another.

They didn't even combine the monotherapy arms into a single number and they still were hitting huge results.

I do not see how they will be able to bluff this one by saying it did not hit the primary.

The real headline was the subgroup result.

 

 

There is another phase 3 in mild AD that should do even better to report later this year.

There is a FTD trial that is to report next month.

 

How can the FDA ignore these results?

The brain scan portion of the trial came back confirming the cognitive and functional results.

 

The combined p value in this trial could simply be staggering!

Dismiss a p value of 1 in 100,000?

When treatments are clearly ineffective that is one thing.

What happens when a treatment for some unexplained reason clearly is effective?

What legitimate process exists to deny patients a treatment then?

 

 

We simply might have reached an AD trial where the verdict has already been reached.

If the FDA decides to ask for yet more trials, then people might simply ignore them.

 

Of course, the mice studies found that tau neuropathology was a universal biological process.

Are normally cognitively ageing people also going to ignore these results?

 

LMTX has been shown to be safe, and there is considerably suggestive evidence that this is effective in AD.

Right to Try?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Edited by mag1, 28 July 2016 - 01:35 AM.

[Logic]

People! People! Please!

 

Methylene Blue is looking like it is the one.

They stopped NEARLY COMPLETELY STOPPED progression of AD in mild to moderate patients over the 15 month treatment interval.

[Might not be as popular as logic, though when the dam breaks ole mag1 will capitalize, underline, highlight in neon red and if I could

surround in purple polka dots. Mag1 goes the extra mile for the people!]

 

(Difference in ADCS-ADL decline was almost 7 points. This is the typical change over the course of a year. So over the 15 months

we would have been looking at 8.75 point change expected. LMTX is preventing 7 of 8.75 points of the decline. Not bad!) 

 

This is large news.

Still somewhat clear about how small the subgroup of monotherapy patients was, though even so this is BIG.

 

Comments please!

 

Could someone get a delegate at the ICAD conference in Toronto to turn their cell phone on at the presentation today between 4:15 - 5:45 PM?

The whole world is watching!

The people have a right to know!

 

I am flattered that I am considered so popular Mag1!?

I also value your input and insights here.

 

MB is big IMHO.
Leuko MB is even bigger IMHO.  (Thats MB that's been reduced with Ascorbic Acid.  It's clear = less messy, easy to make, and better anti AD results were seen with it IIRC ?

Another important consideration (perhaps the missing link!?) is Turnbuckles take on MB IMHO.

8. Methylene blue & niacin & Alzheimer's:

 

A few years ago (after the stories about Rember came out) I tried a dose of MB. I didn't have Alzheimer's but it seemed like a potentially good prophylactic as everyone my age probably has some of this defective tau protein. In fact, I found that I was thinking more clearly with a dose of 100mg, but when it wore off I was suddenly having difficulty following the plot of TV shows. Uh-oh! So I looked for something that would correct the defective (hyperphosphorylated) tau that causes tangles and tried MB again a couple of days later, this time adding 500 mg niacin every few hours. The problem went away and when the MB wore off I was no worse off for the experience. So I realized that seemingly modest doses of MB can be dangerous, that even if you don't have symptoms of AD you might create them by forming large tangles that didn't previously exist, as the largest tangles will grow at the expense of smaller ones. On the plus side, it seemed possible that MB+niacin is a cure for AD, if the MB dissolves the hyperphosphorylated tau tangles and allows niacin (or niacin analogue like niacinamide) to get access.

PMID: 18987186 -- "These preclinical findings suggest that oral nicotinamide [niacinamide] may represent a safe treatment for AD and other tauopathies..."

Other supplements that have been shown to mitigate tau pathology: sodium selenate and propranolol. I take both.

http://www.longecity...769-turnbuckle/

Also search for his many posts on the subject here.

 

I also note that both MB and Niacin seem to be involved in optimal mitochondrial/NAD+ function and wonder how this relates to misfolded proteins etc?
I do know that Mitochondria are high in sulphur bound iron, and that iron reacts violently with the acids in lysosomes, damaging this last stage in the 'junk recycling production line'.

So perhaps MB and other mitochondrial enhancers result in less defunct, recycled mitochondria, decreasing the amount of iron that ends up in lysosomes before they can be replaced..?

 

Information on iron in mitochondria and how light unbinds it and causes sunburn (and skin aging?) can be found in the Tiron thread:

http://www.longecity...ed-antioxidant/

 

Given that excess iron is implicated in dementias, skin aging and AGE formation (= inflamaging),  I am surprised at the lack of interest in Tiron and other chelators like M30 and Black Sesame seed Pigment.

 

Also; MB is an antifungal and an antibacterial IIRC, and that biofilm forming, autophagy blocking bacteria have all been associated with dementias...

 

Edited by Logic, 28 July 2016 - 11:39 AM.

[resveratrol_guy]

I think Turnbuckle was onto something with his niacin coadministration theory. I've come around to the notion that steady NAD+ production is much more important than the size of any particular dose of a NAD+ precursor such as niacin or niacinamide or nicotinamide riboside. So personally, I take choline with inositol, Niagen, and Longvida all at once, 2 to 4 times per day. (I'm thinking of adding cat's claw to this booster regimen, but that's another story.) Anyway, this is just to say that people who megadose B vitamins or NR might be on the right track, but they're risking liver harm and ultimately not helping NAD+ production much, as compared to people who dose small amounts of precursors throughout the day. (Niacinamide is great at bedtime because it's slow release NAD+.)

 

I'm a bit suspicious of the observation that patients already on other AD drugs did not respond to MB; only those not on other drugs did so. While most AD drugs from Big Pharma are marginally effective, they don't appear to be detrimental to memory. So I'm leaning toward MB being useless, and the conclusions of the study being due to small N. The P values look great, but I wonder if they actually did the math right. The results don't make logical sense.

[TRUGAN]

 

Not sure about that helper phage but I am attempting to isolate the m13 from sewer water. I am still in the process of collecting needed supplies. The refrigerated centrifuge seems to be the only equipment needed and I have just received that from ebay and of course it doesnt work as advertised but I have identified the issue and have parts on order to repair. Hopefully I will be making the first attempt in 2 or 3 weeks.

 

One thing to consider is if enough of the phage can travel up the nose to do any good. Maybe if its snorted every day for a long period of time.

 

 

My hat is of to you mrwhitee!

I have not gone into how the phage is isolated/purified from all the other pathogens in the drain water?

 

 

 

Here are a couple of videos that might help. They used the K07 helper phage in this video which is probably better/easier than messing around with the sewer water since the k07 is  already antibiotic resistant but the process should be the same. With the K07 you could grow a really high titer rate quite easily.

 

 

stage 1

 

stage 2

 

 

However, it seems to be unclear whether removing these tangles will benefit any of the neurological diseases but this could be the safest/easiest way to try it. I wonder if it would be worth it for prevention . Perhaps stopping the tangles to start with would be beneficial but some people have the disease without any of the tangles so I dont know what to make of all that.

Edited by mrwhitee, 29 July 2016 - 03:57 AM.

[Kalliste]

How does dental X-rays compare to CT-scan in terms of total radiation? I'm going to see if I can google that up because I could X-ray my brain at work

 

Never mind, I found a chart, catching up with CT using a dental X-ray seems a bit bothersome to say the least

 

Attached Files

•  Namnlös.jpg   301.15KB   5 downloads

Edited by Cosmicalstorm, 29 July 2016 - 11:59 AM.

[Logic]

I think Turnbuckle was onto something with his niacin coadministration theory. I've come around to the notion that steady NAD+ production is much more important than the size of any particular dose of a NAD+ precursor such as niacin or niacinamide or nicotinamide riboside. So personally, I take choline with inositol, Niagen, and Longvida all at once, 2 to 4 times per day. (I'm thinking of adding cat's claw to this booster regimen, but that's another story.) Anyway, this is just to say that people who megadose B vitamins or NR might be on the right track, but they're risking liver harm and ultimately not helping NAD+ production much, as compared to people who dose small amounts of precursors throughout the day. (Niacinamide is great at bedtime because it's slow release NAD+.)...

 

You may want to look at the effects of Inositol on autophagy here (and subsiquent posts) RG:

http://www.longecity...ndpost&p=763863

I have moved any inositol intake to the morning.

 

I am also a big fan of HGW.

[resveratrol_guy]

 I'm going to see if I can google that up because I could X-ray my brain at work

 

Be careful. You could end up with asymmetric exposure if you don't track things accurately. (I guess you could use random alignment). Also you might irradiate your coworkers (which would be unethical even though they might live longer) if you're not using a lead apron behind your skull, or you're reflecting the xrays off a hard surface.
 

If LLLT is any clue, you might want to do this at most every couple days.

 

Your idea is totally crazy, but I must admit that it sounds like it would work, after a while.

[resveratrol_guy]

You may want to look at the effects of Inositol on autophagy here (and subsiquent posts) RG:

http://www.longecity...ndpost&p=763863

I have moved any inositol intake to the morning.

 

I am also a big fan of HGW.

 

Well now that's interesting. I had no idea inositol had anything to do with autophagy. It just happens to come packaged with the choline. Maybe what I really need to do is stop taking supradietary doses, and just get plain old choline.

 

OTOH, it might not matter too much in my case because I'm taking a panoply of growth inhibitors as it is, and there is a point at which autophagy causes neurodegeneration. IIRC, lithium and sodium valproate are susceptible to this problem at certain high doses. Which is just to say that a little autophagy suppression is probably acceptable. I need to check the dose, though. Thanks for bringing this to my attention.
 

[resveratrol_guy]

However, it seems to be unclear whether removing these tangles will benefit any of the neurological diseases but this could be the safest/easiest way to try it. I wonder if it would be worth it for prevention . Perhaps stopping the tangles to start with would be beneficial but some people have the disease without any of the tangles so I dont know what to make of all that.

 

I don't think anyone without tangles has the same type of Alzheimer's as someone with tangles, the latter being the usual case. Nontangled Alzheimer's might for instance be due to actin decay resulting from mercury poisoning. And the people with tangles who are asymptomatic are probably just benefitting from greater redundancy (hence the association between more years of education and later disease onset).

 

Again, though, what matters most is "unlocking" the tangles with GP3. It seems to render them unable to spread in the usual viral misfolding manner. If we remove that possibility, then we have the challenging but vastly simpler task of maintaining cognitive health via neuroplasticity, immune modulation, neurochemical support, and ultimately stem cell therapy.

 

It should motivate us that supercentenarians have existed who were for all practical purposes cognitively normal -- with no help from Big Pharma. There is a way to do this, and the first step is to pour water on the fire of fibrilization.

 

I wouldn't mind volunteering to try your K07 culture myself, but I don't think I'd be an ideal candidate.

 

[Der Springende Punkt]

In my opinion LMTX and in general MB is dead. Alzforum lists several reasons why the subgroup analysis for the monotherapy group is completely meaningless:

http://www.alzforum....not-work-period

[Kalliste]

 

 I'm going to see if I can google that up because I could X-ray my brain at work

 

Be careful. You could end up with asymmetric exposure if you don't track things accurately. (I guess you could use random alignment). Also you might irradiate your coworkers (which would be unethical even though they might live longer) if you're not using a lead apron behind your skull, or you're reflecting the xrays off a hard surface.
 

If LLLT is any clue, you might want to do this at most every couple days.

 

Your idea is totally crazy, but I must admit that it sounds like it would work, after a while.

 

 

I was mostly joking, besides as the chart shows it would take an absurd amount of time to come anywhere close to the total CT dose. Obviously I never use X-ray with anyone innocent nearby, we have rules for that. And the rays adhere the inverse square law so even if we didn't have walls they do not go further than a few meters. We also have ventilation that removes whatever tiny amount of ionized air that is created.

Edited by Cosmicalstorm, 30 July 2016 - 08:56 AM.

[mag1]

res, it looks like you called it right: They didn't do the math right.

 

taurx compared those on LMTX who did not feel it necessary to take Alzheimer's drugs because they were non-progressors or did not have Alzheimer's in the first place

to those not on LMTX who did feel it necessary to take Alzheimer's drugs because they were progressors (possibly rapid progressors).

 

Under such a study design any "treatment" would be expected to do better than placebo.

With such a scenario, 1 in a million p values and a positive primary endpoint readout on the monotherapy subgroup on the second phase 3 trial notwithstanding, the trial cannot claim success.

 

I have been fooled a few times on small subgroup analysis (for example,  the bapineuzumab phase 2).

This is the first time that I have been fooled on a positive primary analysis. (taurx confirmed that the second phase 3 will use the LMTX monotherapy as a primary endpoint.

They have also said that this LMTX monotherapy subgroup also saw benefit relative to the placebo group treated with standard of care.)

 

This could be an exercise in pathological science.

taurx might proclaim success in the primary analysis in a phase 3 trial, without it actually being a success.

 

That has brought us nearly up to date.

The new twist is that taurx also said that they intend to combine the monotherapy and untreated placebos in the two phase 3s to see if there were a treatment effect.

Such an analysis would have approximately 100 patients on monotherapy LMTX and perhaps 80 on untreated placebo.

 

I am very unsure how one could rebut a positive response to such an analysis, if it were to occur.

The two arms- LMTX monotherapy and placebo non-treated- would be blinded.

 

There is an open label extension trial that has been accruing for 2 years now and is expected to enroll 1000 patients.

All those on the open label are being treated with LMTX.

If they simply ask the patients not to take standard of care while on LMTX, then it would become rapidly apparent whether LMTX were effective or not.

Of course asking these patients to do so would not be ethical if LMTX were known to be ineffective.

 

One problem, though, with the extension trial is that they do not appear to have continued with the mental status tests.

If they are serious about determining whether LMTX is effective, then they need to restart the cognitive testing (ADAS-Cog, ADCS-ADL ...).  

 

Given how large the treatment effect has claimed to be, we should know fairly soon whether LMTX is effective or not.

taurx could also start a smallish and shortish follow-on study that could clarify the results of the phase 3 trials.

 

 

 

 

Edited by mag1, 30 July 2016 - 02:30 PM.

[mag1]

http://seekingalpha....-success?page=1

 

 

As of yesterday taurx was not moving away from its position.

 

"the first thing that was done was to look at the decline in the control arm, but this was found to match

the control arms of similar phase III studies with solanezumab and bapineuzumab."

 

taurx "expects to report an unambiguously positive result for the second study"

 

"the company’s advisors suggest that it could file on the basis of the yet-to-be-reported TRx-237-005 with supportive data from TRx-237-015."

Fortunately "the full data will soon be published in a peer-reviewed publication"

Edited by mag1, 30 July 2016 - 08:36 PM.

[mag1]

We might have missed this sleeper from the Toronto ICAD: CPC-201.

Quadruple strength Aricept. 90% response rate in mild to moderate Alzheimer over 26 weeks of treatment.

(response means no progression).

 

Fairly interesting idea.

By cotreating with solifenacin, the side effects in the body are blocked but not in the brain because solifenacin is not brain penetrable.

 

http://www.alzheimer...-donepezil.html

 

[Der Springende Punkt]

We might have missed this sleeper from the Toronto ICAD: CPC-201.

Quadruple strength Aricept. 90% response rate in mild to moderate Alzheimer over 26 weeks of treatment.

(response means no progression).

 

Fairly interesting idea.

By cotreating with solifenacin, the side effects in the body are blocked but not in the brain because solifenacin is not brain penetrable.

 

http://www.alzheimer...-donepezil.html

 

This one has probably the best chances for an approval atm even when it might lack disease modifiying properties. Given the weak current treatments CPC-201 would be a major improvement.

[TRUGAN]

 

However, it seems to be unclear whether removing these tangles will benefit any of the neurological diseases but this could be the safest/easiest way to try it. I wonder if it would be worth it for prevention . Perhaps stopping the tangles to start with would be beneficial but some people have the disease without any of the tangles so I dont know what to make of all that.

 

I don't think anyone without tangles has the same type of Alzheimer's as someone with tangles, the latter being the usual case. Nontangled Alzheimer's might for instance be due to actin decay resulting from mercury poisoning. And the people with tangles who are asymptomatic are probably just benefitting from greater redundancy (hence the association between more years of education and later disease onset).

 

Again, though, what matters most is "unlocking" the tangles with GP3. It seems to render them unable to spread in the usual viral misfolding manner. If we remove that possibility, then we have the challenging but vastly simpler task of maintaining cognitive health via neuroplasticity, immune modulation, neurochemical support, and ultimately stem cell therapy.

 

It should motivate us that supercentenarians have existed who were for all practical purposes cognitively normal -- with no help from Big Pharma. There is a way to do this, and the first step is to pour water on the fire of fibrilization.

 

I wouldn't mind volunteering to try your K07 culture myself, but I don't think I'd be an ideal candidate.

 

 

 

I found a lab that will make the phage and purify it for human use at a cGMP site but it is costly. Around 4000.00. Anyway, if someone believes that removing these tangles will help then 4000.00 isnt bad. The costly part is for them to remove the endotoxins created from the destroyed bacteria and some other junk from the culture material.

[resveratrol_guy]

 

We might have missed this sleeper from the Toronto ICAD: CPC-201.

Quadruple strength Aricept. 90% response rate in mild to moderate Alzheimer over 26 weeks of treatment.

(response means no progression).

 

Fairly interesting idea.

By cotreating with solifenacin, the side effects in the body are blocked but not in the brain because solifenacin is not brain penetrable.

 

http://www.alzheimer...-donepezil.html

 

This one has probably the best chances for an approval atm even when it might lack disease modifiying properties. Given the weak current treatments CPC-201 would be a major improvement.

 

 

Personally I'm not a fan of ACHi's because they just mask ongoing neurodegeneration by providing more acetylcholine. When they stop working, the decline is precipitous. Granted, there are few other options out there, and none particularly effective, but the bottom line is that we need to improve NAD+ availability, dissolve plaque, inhibit the fibrilization chain reaction, support cerebrovascular competence, and spur neurogenesis.

 

In theory, pharmacological support of neurotransmitter levels would surely enhance connectivity, so in that sense, there would be more connections to destroy. This is probably why more educated people resist dementia for longer. So in that sense I support this kind of approach, but I would start with the foregoing more fundamental considerations.

 

I think you explained the MB results quite well. It's a statistical mess, unfortunately, and even if it does work in some cohorts, the problem is always going to be trying to predict who will benefit and who won't. At least, we still have LLLT, which costs $20 for the apparatus and $10 for all the electricity it's going to use over a lifetime!

[resveratrol_guy]

I found a lab that will make the phage and purify it for human use at a cGMP site but it is costly. Around 4000.00. Anyway, if someone believes that removing these tangles will help then 4000.00 isnt bad. The costly part is for them to remove the endotoxins created from the destroyed bacteria and some other junk from the culture material.

 

I don't think that's expensive, if it shuts down the disease progression and only needs to be repeated every few years.

 

Please clarify: are you talking M13K07 or "plain vanilla" M13 or both? In what country is this lab?

[mag1]

res, the statistical mess with LMTX is only going to get messier.

taurx now has a lock on reporting a positive primary analysis on the second phase 3 in mild AD.

If they use the same statistical approach as they did in the first trial, we will all know a priori that the result is meaningless.

 

Everything could of course become quite interesting.

For example, it would only take 100 amyloid scans to prove that the LMTX monotherapy subgroup did in fact have amyloid pathology.

If taurx does not bother with these scans during the next 6 months, then they will have admitted that those patients did not in fact have Alzheimer's. If the combined monotherapy LMTX versus untreated placebo reads back positive, I would also be unsure what to make of it. 

 

Best strategy here is just to play it cool. We should have a clear answer to this within a year. There's $100 billion on the table for taurx,

it's time for them to ante up. It will be very interesting to see on the next bidding round whether taurx puts more money into the pot.

The results that taurx are suggesting are so large that it will not be difficult to confirm or refute over a reasonable time horizon.

 

My first worry when the results came out was that confirmation would require years and years. Slowing progression by 80% will not require a 5 year trial to verify. The sooner they start a mini-phase 3 trial with 100 on monotherapy and 100 on control the sooner we'll know for sure. This time they should do the trial right with amyloid imaging and perhaps full genome scans.  

 

I think I am with Der SP on CPC-201. Sure we all want to see one launched out of the park, though I'll take a respectable standup double. CPC-201 uses a smart idea to avoid side effects and to create a powerful anti-dementing drug. I looked over the treatment results with Aricept, and at 10 mg the cognitive benefit was only modest. However, by dosing up to 40 mg Aricept with 15 mg solifenacin (CPC-201) over 90% of patients with moderate AD were stabilized for 6 months. It is quite remarkable that Aricept helps those with mild, moderate and severe AD. I will be very interested to see how the phase 3 trials turn out for CPC-201. I would be especially interested to see whether they use a treatment to failure design. It is reasonably clear that CPC-201 should show benefit over a 6 month treatment period. What I would love to see is for these patients and the trial to continue until the drug was no longer effective. The company could be allowed a marketing claim for the period of time in which CPC-201 helped patients. As it is now, I am not sure whether Alzheimer researchers would necessarily have a good idea of how long the treatment effect would last. 

 

It might not be disease modifying, though in the history of AD clinical care there is nothing that has ever approached those numbers (aside from LMTX). Interesting that nearly all the media attention was on LMTX and not on CPC-201.  

Edited by mag1, 31 July 2016 - 10:01 PM.

[TRUGAN]

 

I found a lab that will make the phage and purify it for human use at a cGMP site but it is costly. Around 4000.00. Anyway, if someone believes that removing these tangles will help then 4000.00 isnt bad. The costly part is for them to remove the endotoxins created from the destroyed bacteria and some other junk from the culture material.

 

I don't think that's expensive, if it shuts down the disease progression and only needs to be repeated every few years.

 

Please clarify: are you talking M13K07 or "plain vanilla" M13 or both? In what country is this lab?

 

 

 

The lab is in Poland and they use the M13K07 and it displays the GP3 protein the same. The price is for 1 ml with a titer that  I requested to be  between 10^11 to 10^13

 

price was quaoted at about 3500 Eur

Edited by mrwhitee, 01 August 2016 - 10:16 PM.

[TRUGAN]

If we had more people interested I could maybe get a better quote. Do we have many people interested?

[albedo]

Here is an intriguing approach. While results are anecdotal, definitively the approach should warrant an extensive trial.

 

Results from the 10 patients reported “…suggest that memory loss in patients with subjective cognitive impairment, mild cognitive impairment, and at least the early phase of Alzheimer’s disease, may be reversed, and improvement sustained, with the therapeutic program described here. This is the first such demonstration...” (bold mine)

 

Beside the impressive results, I particularly liked the basic tenets of the approach:

• Metabolic parameters optimization vs. normalization
• Combination vs. mono-therapies
• Threshold effect leading to reversal of the impairment
• Personalized

 AD Therapeutic System 1.PNG   75.23KB   6 downloads

 

Reversal of cognitive decline: A novel therapeutic program

http://www.ncbi.nlm....les/PMC4221920/

 

“This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer’s disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3‐6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow‐up is two and one‐half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.” (red mine)

 

 

[Mian Ali Ismail]

COGNITIVE IMPROVEMENT WITH INTRATHECAL ADMINISTRATION OF INFLIXIMAB IN A WOMAN WITH ALZHEIMER’S DISEASE ! ! !

 

http://doc.sciencene...19584414614.pdf

[albedo]

I though useful to post this also in this thread (from the Pentraxin's web site):

 

Strong experimental support for the DESPIAD trial of CPHPC in patients with Alzheimer’s disease

https://pentraxin.wordpress.com/news/

 

[Mian Ali Ismail]

Is this true 

 

There have been several reports that anti-tumor necrosis factor alpha (TNFa) agents may affect amyloidosis in inflammatory disease, such as rheumatoid arthritis and familial Mediterranean fever.2,3 Rapid cognitive improvement after perispinal etanercept administration had been reported.4,5 This may be the first report to suggest an effect on Ab/p-tau in a person with AD by anti-TNF. Similar results were obtained in animals.6,7 A previous study indicated that intracerebroventricular administration of infliximab reduced amyloid plaques and tau phosphorylation in APP/PS1 mice.8 The case report suggests the pivotal role of TNF-a and the interaction between TNF and amyloid in the pathogenesis of AD. The efficiency and safety of infliximab need to be researched further in large sample trials or randomized control trials. The current results suggest that intrathecal infliximab offers a superior alternative therapeutic approach for AD and potentially for other neurodegenerative disorders in which TNF-a is involved in the pathogenesis, such as Parkinson’s disease and amyotrophic lateral sclerosis.

 

 

There is also a DR, in US who claims tht perispinal entrancept also works through tumor necrosis factor  and has treated several patients.