pbt2a analysis by ty.webb

Found this on another forum (SS) and thought it would be worthwhile sharing here. This guy knows his stuff:

I'm expecting the results to be released in late February (just an educated guess). I'm also expecting the announcement to declare the trial a success - although just how big a success remains to be seen. The indications are that safety and tolerability will be established at both doses. That leaves us with the biomarkers and the cognitive tests.

The biomarkers are meant to show whether PBT-2 is actually hitting its target. Now given that AD biomarkers are inherently stable, and that in this particular trial changes are being measured in each patient from baseline, and that the people running the trial are experts in the field of AD biomarkers, its a pretty simple proposition: does PBT2 actually mess with beta-amyloid? I'm willing to bet strongly that it does, and that the results will confirm this by showing clear-cut biomarker changes in the treatment arm while the placebo patients show stable levels.

Rudi Tanzi was talking about this recently with Colin Masters and they agreed that if PBT2 couldn't be shown to be hitting its target, then they would both be prepared to abandon the beta-amyloid hypothesis entirely - which is quite something when you consider that Masters is one of the founding fathers of the hypothesis.

Of course, its one thing for PBT2 to hit its target - its another thing to show that this activity is of any benefit to AD sufferers, as Neurochem found out recently with Alzhemed. What will the cognitive tests show?

This is the wild-card. Generally speaking, recent trials of other promising interventions have shown that disease stabilisation is certainly possible if you can mess with beta-amyloid, with the effects being more noticeable the longer that treatment goes on. But the PBT2 Phase 2A trial was of relatively short duration. Will it be able to show anything of significance?

I think the answer here is definitely "yes". The reason is that PBT2 promises to fight AD on the battle-field that really matters - at the synapse and against the toxic oligomers that accumulate there and are now being increasingly recognised as the true villains of the story.

There are two "ifs" involved here - if the acculumation of toxic oligomers at glutamergic synapses is what causes memory loss in AD patients, and if PBT2 can blast these oligomers where they do the real damage (where copper and zinc ions are released as part of neurotransmission), then its possible that PBT2 could do far more than just stabilise disease progression - it could actually reverse memory loss. This is what I mean about the "wild-card".

If we cast our minds back to July 2006, we may remember the day that PBT exploded to an intra-day high of 80c, after closing the previous trading day at 19c. That amazing flurry was caused by comments attributed to Professor George Fink, the director of the Mental Health Research Institute of Victoria. In brief, what Professor Fink said was that if Prana
could replicate in humans what it had achieved in mice, then AD would be a thing of the past. Prana released a statement the following day to hose down expectations, but I think it may literally pay now to recall the enthusiasm of Fink's original remarks. What Prana achieved in its animal trials at about that time was truly remarkable - the transgenic
Alzheimer-model mice that were treated with PBT2 actually performed better in the water maze tests than the healthy controls. The effects of treatment with PBT2 were both rapid and profound and far exceeded anyone's expectations.

This leaves open at least the possibility of a similar result in humans.