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Biotech / Medical : SIBIA Neurosciences (SIBI)
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To: scaram(o)uche who wrote (120)11/19/1997 11:09:00 PM
From: r. peter Dale  Read Replies (1) of 579
 
Rick:

I promise not to lay on too much neuroscience nuts and bolts but I am curious: you indicate the anti-AchE approach is 'proven'. Could you elaborate, to wit:

1) I assume you're referring to well controlled cognitive evaluation studies. Are you familiar with how these studies were run: since the inhibitors won't effect disease progression, they must ultimately fail (by failure I don't mean death - rather the cholinergic population has been reduced to such a degree that even 'heroic' AchE inhibition intervention would fail to provide sufficient Ach).

2) I'm trying to recall the muscarinic vs. nicotinic issue that - if I'm remembering correctly - pertains to Sibia's compounds. Are the proven results related to the receptor issue or is the approach to globally inhibit AchE? Also, and I'm really showing my ignorance here, how is it that there are no side effects since Ach is critical at the neuromuscular junction (nicotinic) and some of the most potent nerve poisons are cholinesterase inhibitors?

So, in short (!), what is the nature of the proven results, are they relevant for just for a subpopulation of AD patients, and how do these drugs achieve their specificity? Outside of AD, isn't long term treatment with AchE significantly hazardous to your health?

In lieu of responding you can indicate some refs or the locale of posts where you or others have discussed this. Thx

Best wishes,
Peter
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