Comment by throwawaymaths
2 days ago
he was not in the trenches in 2003. in 2003 we were working in an Alzheimer's lab and everyone in our lab at least was expressing suspicion that there was something wrong with the hypothesis. pretty much every internal lab meeting started with "the amyloid hypothesis is... [this statement exists because our funding stream] though it is not conclusively proven, wink wink"
Granted, I have heard a scientist (in an unrelated field, I think it was some astronomical NPR interview) describe science as a bit like a supertanker...there usually is some prevailing thing that everyone believes in, but as contrary evidence piles up, the direction slowly turns.
I guess my own question is whether Alzheimer's/amyloid thinking was atypically stuck on one hypothesis, vs. is this just the slow pace of progress as usual for a given field? I mean...it's not like the amyloid deposition isn't there...
I only play a AD expert on TV (haha I jest...I like to say this because I had no intention of specializing in this when I was training but, hey, in the real world, you have to treat the "market" that rolls in the door....). I work more in the Parkinson's world, and while I would say there are cliques, which do affect who gets NIH (or used to get...I have no idea what's going on there now...), I can't say there's one prevailing "cabal" that's obsessed with any one direction. the bigger issue is that current Parkinson's research is a bit scattershot in too many directions.
My other pet peeve is somewhat unrelated, where the article mentions other directions like neuroinflammation and oxidative stress; the problem is these are also vague/broad topics, that have been thrown around like panaceas for every disease from head to toe; my own superstition is that when a new drug candidate comes out for "neuroinflammation" or "oxidative stress", I'd bet a healthy bunch of nickels it won't amount to much.
Do you see any curative Parkison (not even reversing the damage but stopping it) treatment being available in the next few years ?
in short, and off the top of my head, not in a few years.
GLP-1 (exenatide trial) failed to show benefit Phase 3
prasinezumab (synuclein targeted monoclonal ab) also have not been impressive although I think Novartis is chasing after some statistical signals that popped up in secondary endpoints
there is some academic chatter I heard about elucidating more the process of how normal synuclein turns into the abnormal insoluble form, so that might be the most promising direction.
A couple new stem cell implant trials but not sure if they solved the big problems w/ the last trials - the stem cells eventually develop parkinsonian features, and also it doesn't replace the connectivity/networks that is lost.
Other big question is really what starts the process in the first place since symptomatic patients at initial diagnosis now thought to have been "preclinical" w/ prodromal form for several years...we still don't know.
His blog has a category just for discussing Alzheimer's, and he's been talking about ever since he started blogging. So here's a post from 2002 where he points out (somewhat obliquely) that amyloid isn't a proven hypothesis: https://www.science.org/content/blog-post/alzheimer-s-vaccin...
> This is looking like one of the crazy ideas that just might work - stipulating, for the moment, that amyloid really is the cause of Alzheimer's. . .
I'm not sure we knew this in 2002 but antibodies are proinflammatory, possibly as a result of their catalysis of ozoniation reaction.