Well, the NYT has weighed-in on the FDA "lowering the bar" for the approval of AD drug candidates. I know we've covered this already, but it is becoming clearer to me that this action is very much a gift for big pharma to allow dusting off prior their safe failures to look for any statistically supportable efficacy, as much as the FDA bending for lack of seeing an alternative. It is as if the FDA has deemed that disease modifying approaches appear to be "not possible". Hopefully, this policy will result in actually expediting a disease modifying candidate that would become the standard of care, supplanting marginally accepted, albeit safe treatments. My opinion, and that is all it is - with some $$$ behind it - is that PBT2 just MAY be in that candidate.
IMO, if PBT2 does show positive efficacy, based on it's mechanism (vs. the MAB, ACH approaches) it will likely not be so subtle. In humans, we know there is good BBB movement; we know abeta increases in CSF within 6 months; and most importantly the metal "chaparone" properties of the compound seem to work in vitro and animal studies based on it's affinity to specifically incorporate or shed the target zinc species based on exposure to abeta plaque, neuronal entanglements or cerebral fluid. It would seem to be a difficult mechanism to disrupt if the PBT2 is maintained at suitable concentration.
Not to belabor this, but PBT-1 was modified into PBT-2 in part to improve BBB transport, to increase the dose fraction that becomes available within the brain. Generally means less has to be administered for the same effect and a lower risk of potential adverse side effects (e.g. liver damage from metabolites).
PBT2's orally taken drug is proven to cross the Blood-Brain-Barrier and act on the areas of the Brain that is affected by AD, HD & Parkinson's. Many compounds fail because simply because they do not cross the blood-brain-barrier and are fought off by the bodies own defense mechanisms as an intruder. Some of the other med's being promised for Neuro-degeneration must get there through other means. Such is the case with the Gene Silencing that shows so much promise for HD - how they are getting it to the effected areas of the brain is in itself among the challenges.