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Member of FDA’s expert panel resigns over Alzheimer’s therapy approval:
Following the Food and Drug Administration's polarizing authorization of the Alzheimer's therapy Aduhelm on Monday, a member of an agency advisory committee that recommended against the drug's approval has resigned.
Neurologist Joel Perlmutter of Washington University in St. Louis, a member of the FDA's expert panel for nervous system therapies, told STAT in an email that he had quit the committee on Monday "due to this ruling by the FDA without further discussion with our advisory committee."
The advisory committee, which convened in November, couldn't have been more openly skeptical of the drug, also known as aducanumab. Ten of the 11 panelists found that there was not enough evidence to show it could slow cognitive decline. The 11th voted "uncertain."
(Score: 5, Interesting) by Samantha Wright on Friday June 11 2021, @11:05AM (4 children)
From TFA:
By "debatable" they mean that one of the studies showed no statistically significant impact, and the other showed an improvement of just 0.18%. It's definitively ineffective.
My guess here is that they're simply too late. Most forms of dementia, including Alzheimer's, involve damage to a group of proteins called tau proteins. In Alzheimer's, it's possibly the case that amyloid causes the damage to the tau proteins before it forms plaques. Tau also seems to be a prion disease that self-propagates and messes up signal transduction in axons (the long part of the neuron that connects its output to the next nodes in the circuitry). The role of tau proteins has been known for a very long time (1976), but with Alzheimer's, big pharma was holding out hope that attacking the amyloid would help. As far as we know the brain functions normally when all amyloid beta is missing, though of course that's a very peak "Chesterton's fence [wikipedia.org]" sort of problem.
I can't think of a good computing analogy that doesn't make it really messy, but basically: thing AB sometimes malfunctions, causing damage to everything, including itself and another thing, called thing T. Thing AB then piles up in big heaps. The drug removes the big heaps. Unfortunately, when thing T is damaged, it also damages itself, and thing M. When thing M is damaged, you have dementia. It is unclear whether thing T can be fixed. It is also unclear whether thing M can be fixed. Tragically, we can only detect Alzheimer's when people show signs of damage to thing M, and then confirm it by using lab tests to locate the big heaps of thing AB. If we don't find the big heaps, we just assume it's another form of dementia.
It is possible that this drug could still be part of a treatment for Alzheimer's, but only in combination with drugs that fixes things T and M also.
(Score: 2) by Samantha Wright on Friday June 11 2021, @11:08AM
("thing M" is hyperphosphorylation of microtubules in axons, which tau proteins are responsible for.)
(Score: 2) by PiMuNu on Friday June 11 2021, @11:28AM (1 child)
Thanks. So it sort of sounds like indeed "correlation != causation" i.e. there is a cause - tau proteins mess up signal transduction - and amyloid is an effect; as well as dementia is an effect. Obviously not that simple and hard to disentangle cause and effect in very complicated system with poor instrumentation.
Speaking as someone who has genetic predisposition to Alzheimer's (or at least I think so, I can't quite remember - gallows humour).
(Score: 1, Interesting) by Anonymous Coward on Friday June 11 2021, @02:55PM
Amyloids are the lowest energy conformation for peptides. Without constant effort to clear them and fold proteins properly they will always form. That is why they are elevated in every diseased tissue known to humankind.
If you are feeling very ill, you cant take out the trash and it accumulates in your house. Same thing.
So, its not really correlatiom != causation. They have causation backwards.
Of course at some point too much trash in the house starts to cause its own problems. But your mom coming over and cleaning the trash wont fix the root problem and may end up hiding how bad the problem is from your neighbors so they get sick too. That is why none of these amyloid removing drugs ever work, it is a huge boondoggle.
(Score: 0) by Anonymous Coward on Friday June 11 2021, @04:26PM
I'm not an expert, but to confirm my understanding (and maybe make it more illustrative), maybe this would be an appropriate analogy?
Somebody finds diamonds in ThirdWorldIstan (the AB malfunctions). Then lots of prospectors go flooding in and commence stripmining, leading to lots of pollution (AB piles up in big heaps). The pollution kills the herbivores in the local ecology (AB damages T), which devastates the food chain (T damages M). So we have a wrecked ecology (dementia).
This drug would remove all the stripminers (remove the piles of AB), but doesn't actually fix the fundamental problem of the herbivores and the food chain being dead (T and M are still damaged), hence the ecology is still ruined (dementia still exists).
Is that roughly what you were saying?