Looks like the receptionist and one of the janitors just wasn't cutting it.
p.s. I gave you a thumbs up. Even itm and rkf get one from me every once in awhile.
Why does this board have so little sense of humor? Rhetorical question. Looking at that chart to the right is wearing on everyone.
Back out of the asx300 in September? Sure enough Prana was indeed not rebalanced in Australia. Providing the restriction on 10 percent shelf since still being listed in the asx300. Next Balance is in March. I wonder perhaps how could this not go unnoticed. Do they need someone with better business acumen?
Yes. I think its interesting that Shoulson will be speaking about AD and we've been thinking mostly of him in terms of HD. He had alot to say at the IMAGINE conference call so clearly he had looked at the data. It may be just an introduction type thing for him to speak on behalf of Prana but it could also be more. The extension trial is open label so we could get some information about that. Myself I'm hoping and waiting to hear something about the placebos in the IMAGINE trial.
Sentiment: Strong Buy
Also, I guess there's some temporary mitigation to the oligomer disruption of synapses (and other problems that can come with oligomer formation) when those small aggregates get aggregated into larger formations.
That process of oligomer formation would still continue to occur, even while earlier oligomers are being (or have been) "removed" into larger aggregates.
That wouldn't help in recovering the metals locked into the aggregated amyloid, but it would help to limit to some extent the amount of oligomers affecting synapses.
Of course, that's only a temporary reprieve because those larger aggregates are what form into plaques and later cause damage of their own.
Maybe also because more and more metals are getting sequestered, there's a kind of positive feedback occurring... the more oligomers that form (and are later taken up in plaques), the less biometals are available for their necessary functions... leading perhaps to more problems within the cells...
And I could imagine how that might be a slow process becoming more and more problematic over time... as more and more of the basically fixed supply of biometals metals are sequestered and less and less are available for their biological functions.
(or something like that, at least, perhaps, in part, ;-)...)
I also forget the details of the oligomer-synapse process, but it may be that the disruption to the membrane doesn't stop the nerve cell from firing completely, all at once, but is itself a slower process. Perhaps it reduces the neuron's firing efficiency by 20%, then 40%, and so on. That would make a subtle cognitive effect even more subtle to detect. A real, real slow fade.
Masters' discussion of the soluble oligomers embedding into the synapse, and disrupting the integrity of the membrane is convincing to me. But I'm thinking, like you, that at this stage, the 'reserve' capacity is enough to make the cognitive changes subtle and hard to detect. But if the disease progresses slowly, perhaps these early changes are often written off as 'just getting older'.
Perhaps one reason why so many of the Imagine participants went into the extension is that they sensed a subtle improvement in themselves. Subtle, but noticeable in their daily lives. Maybe not leaving the water boiling on the stove as often, stuff like that.
Ah, yes, I hadn't read your summaries, tb, otherwise I wouldn't have been repeating you in mine, ;-).
On another note, I'm curious about the oligomers having an effect on the synapses, something that happens at the very earliest stages of amyloid aggregation (and continues to happen throughout the course of the disease).
It's fairly easy to understand that it could take a long time for amyloid build-up to contribute to nerve damage via plaque formation, which then triggers other things that need to occur in the course of the disease... and, therefore, a long time for amyloid buildup to lead to cognitive decline via plaque formation.
But if oligomer formation within the synapses (and the trapping of needed biometals) effects the functioning of nerve cells, then why don't we see more cognitive decline in the early stages of the disease?
Maybe it has to do with the "reserve" of brain function that Rudy sometimes talks about, reserve that can be cultivated by learning, a healthy lifestyle that promotes healthy circulation and nutrition, etc. Having (and building upon) such a reserve doesn't serve to modify the course of the pathology, but it makes for more of the brain to draw on. He sometimes uses the analogy of building up savings and having some money in the bank to draw on once other sources have come to an end.
Maybe there's eventually a kind of "critical mass" that occurs with regard to the number of nerve cells affected by these challenges. Maybe at some point, there isn't enough "reserve" to compensate for the impairment occurring among nerve cells.
Still, maybe that oligomer formation and the disruption of synapses (along with the trapping of needed biometals) DOES cause some detriment to cognitive function and is what was shown in the normal aging mice study, but perhaps it is a more subtle decline, more subtle than our current cognitive tests designed for later stages of AD, can readily detect.
Neither Colin Masters nor Rudy Tanzi see Lilly's sola drug as a failure, more of a right drug, wrong time and duration challenge. I still like pbt2 going after metals because that's an important part of more than amyloid buildup prevention. Still, however, its effectiveness would be based on stages of the pathology that are mostly PRE-cognitive decline, and trial's to show modification of cognitive decline would face much the same challenge of Lilly's sola, challenges which are currently virtually prohibitive for even a well financed company to accomplish.
Enter the importance of the work at Tanzi's lab. It's still got a considerable ways to go, but it may eventually help to convince the FDA that showing efficacy at those early stages with those early targets (particularly amyloid, and amyloid and tau for pbt2) is enough to naturally lead to efficacy later, in modifying cognitive decline.
In the mean time, however, before that link is made crystal clear, PBT2 can still get to the market (and to AD patients) by being approved for HD (and prescribed off-label for AD... something that I will most certainly begin asking of any doctor who will listen... once its approved for HD, and the supply is there).
And at this time, when cognitive benefit still needs to be shown in clinical trials for AD, a drug candidate that has another route to market (or is already in the market) is at an advantage.
And so, all eyes (our eyes, at least) are on pbt2 and HD (as well as continued safety data on the IMAGINE patients).
I'd be pleased, by the way, for PBT2 to be given the green light for a confirmatory trial in HD (particularly if the HD community would be willing to help - both with at least a portion of the funds and with recruiting appropriate trial volunteers), although, of course, some sort of approval before a further trial, would be fantastic.