9 replies to this topic

[resveratrol_guy]

How did we miss this last August?

In one of the most thorough Alzheimer's (AD) studies I've ever read, Axon Neuroscience has developed a vaccine, AADvac1, which targets only the pathological forms (plural) of tau protein, which many studies have shown are more conducive to AD pathology than the much-maligned amyloid beta plaque.

Briefly, it appears that the tauopathy proceeds in a manner akin to prion disease, in which misfolded proteins beget more of themselves in an exponentially explosive manner involving several different mutant topologies. This chain reaction gradually disintegrates the microtubules which form the basis of memory.

Part of the answer to this problem involves clearing amyloid beta, which accelerates the process. This has been done with considerable success in previous vaccine trials at the cost of various severe side effects. Modern amyloid beta vaccines are less likely to suffer from these effects, and trials are ongoing. Dietary supplements such as lipidated curcumin and many others may help as well. Nevertheless amyloid clearance is of minor significance in the evolution of symtomatic AD, affecting only speed of progression (except, perhaps, in the very early stages, before the tau chain reaction erupts).

A more effective therapy would appear to involve autophagy upregulators such as rapamycin analogs, wogonin, and others. This would clear tau aggegrates as quickly as they form, preempting the chain reaction, despite the continual reemergence of these hazardous proteins.

But a vaccine which teaches the microglia to recognize the tau epitopes required for accomplishing the chain reaction stands a chance of disabling disease progress on an indefinite basis, at which point, the patient could relearn lost memories from external sources and (eventually) replace the lost white matter with stem cell therapy.

A phase 1 human clinical trial is underway, and has apparently finished recruiting.

Proof that it's a real trial:

https://clinicaltria...how/NCT01850238

Visual evidence of reduced tau population:

http://alzres.com/co.../4/44/figure/F3

Press release:

http://www.axon-neur...ation-final.pdf

Rodent study full text:

http://alzres.com/content/6/4/44
 

[resveratrol_guy]

Bump! I called Axon Neurosciences and asked about their AADvac1 trial linked above. Some key findings:

1. They are "pretty much finished" with the phase 1 (safety profiling) study. (I wish I could buy their stock, but they aren't publicly traded! Then again, if they were, then surely they could never have told me this.)

2. They anticipate phase 2 starting in Europe in 9/2015, plus or minus. This is impressive, being as it is only 3 months after phase 1 is projected to complete, based on their registration at clinicaltrials.gov. So to the Europeans here with family members who meet the phase 1 criteria, this would be something to watch for, as presumably the criteria won't change much.

3. According to the following timeline, they started the process of "humanizing" AADvac2 back in 2013. To me, this is a statement that the company is confident enough in its approach that it sees it worthwhile to operate on the assumption that AADvac1 will prove effective and worthy of further optimization.

http://www.axon-neur...on_brochure.pdf

4. There is no way to buy their vaccine right now, thanks to EU and FDA regulations, so Big Nanny can ensure that patients continue to decline while they spend billions on useless Alzheimer's drugs. But at least, there is this trial.
 

[Antonio2014]

Thanks for the information. Do you know what are the criteria for admission into the trial?

Edited by Antonio2014, 04 March 2015 - 04:04 PM.

[resveratrol_guy]

Phase 1 is no longer recruiting, but if history is any clue, then phase 2 inclusion criteria will be substantially similar. To see the phase 1 inclusion criteria, go here and scroll down to "Eligibility". Anyone who fits the criteria should help Axon Neurosciences get ahead of things by contacting them at their website here (click "Contact") so we can test this promising vaccine with minimum delay. This is one of the few companies targetting the molecular engine at the heart of Alzheimer's, instead of some hopeless approach to temporarily mask the symptoms. If you chat with them, then it would be useful to know if the control group will be allowed to get the vaccine, assuming that it appears to work in phase 2. This would seem to be the most ethical approach.

 

It bears repeating: there's a long list of therapies available to restore lost cognitive function, and relearn lost memories. But unless we shut down the phosphotau prion chain reaction, other therapies will remain palliative as opposed to rejuvenating.

 

For those who can't wait for trials, see this set of graphs from this paper. This was a 2012 study on the effect on Longvida lipidated curcumin in Alzheimer's mice, which showed that it has a therapeutic effect on some pathological tau species, ultimately resulting in cognitive improvement. In particular, see graph A, which shows that treated human tau transgenic mice were able to remember the location of a hidden platform in a Morris water maze just as well as healthy controls, even though their swimming speed was somewhat subnormal; untreated transgenic mice exhibited about double the search time, suggesting memory failure. In further proof of this hypothesis, when the platform was visible, the untreated transgenic mice were able to reach it in half the time, demonstrating that the delay in Graph A was not merely due to motor or muscular deterioration.

 

Edited by resveratrol_guy, 05 March 2015 - 04:05 PM.

[Antonio2014]

Thanks. After reading it, it seems that it will only be available to German-speaking Austrians. The person I wanted to suggest this doesn't satisfy any of the two requisites :(

[ceridwen]

It's not currently recruiting

[resveratrol_guy]

"The Phase I study in humans has confirmed that AADvac1 is safe and well tolerated. It induced a robust immune response and the cognition of the patients remained on average stable for the whole duration of the Phase I study."

 

"We are excited to present the official start of the Phase II study with the first patient already screened on March 9th, 2016."

 

http://www.axon-neur...se-aat-2016.pdf

[Daniel Cooper]

Any updates on this Tau vaccine?

 

 

 

[jondoeuk]

Any updates on this Tau vaccine?

Just this https://www.ncbi.nlm...pubmed/27955995

 

Also a new study is recruiting participants https://clinicaltria...how/NCT02579252

[resveratrol_guy]

Axon Neuroscience announced phase 2 results in April, as I just happened to notice today. I think it's not unreasonable to say that this looks to be the single the most effective monotherapy to date. It definitely has a future in multifactorial Alzheimer's therapy.