SoylentNews is people
SoylentNews
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: 2) by PiMuNu on Friday June 11 2021, @09:53AM (13 children)
Interested in why the drug doesn't work. Is it just that they didn't run the trial for long enough? Or is it that the Amyloid theory is wrong (correlation != causation etc)?
(Score: 0) by Anonymous Coward on Friday June 11 2021, @10:32AM
From what I've read the main study didn't show correlation so they cherry picked a few cases from another group that sorta did if you squint.
(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?
(Score: 1, Interesting) by Anonymous Coward on Friday June 11 2021, @11:12AM
A very smart doctor/researcher in that field that I am slightly acquainted with is adamant that the amyloid plaques are the result of Alzheimer's, not the cause.
He does say that an effective and non-damaging amyloid removal would provide some symptomatic relief, and delay the apparent progress of the disease, but it is not a cure.
(Score: 3, Interesting) by HiThere on Friday June 11 2021, @01:19PM (2 children)
Probably the Amyloid theory is wrong. Every attempt based on it has been a dismal failure. The problem is that there *isn't* a decent theory of what causes it.
One plausible theory that I've heard is that it's due to weakening of the blood/brain barrier. Something in the blood stream starts slipping into the brain. This is, IMNSHO, now more plausible than the Amyloid theory. The plausibility is, of course, largely, of course, because it hasn't really been checked out. After it's been investigated thoroughly it may turn out to be less plausible.
Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
(Score: 0) by Anonymous Coward on Friday June 11 2021, @03:07PM (1 child)
There is a decent theory that lead to beneficial drugs: the cholinergic hypothesis.
For some reason this was abandoned in the 1980s in favor of the amyloid hypothesis, which became dogma even though that one has never lead to anything. Now, 35 years later, we get this farcical FDA approval.
Medical research is becoming more pathetic every generation and it is accelerating.
(Score: 0) by Anonymous Coward on Friday June 11 2021, @05:26PM
"Zzzzzzz... more research? Boring! Just give me something I can sell for fuck's sake. I can't sell you telling me things don't work. So just give me something, anything. I'll get it out there, you'll get a big fat bonus, and we'll all go home happy."
Aren't MBAs great.
(Score: 2) by VLM on Friday June 11 2021, @07:09PM
That science stuff doesn't matter any more. The problem is you set up a revolving door system where corporate execs take turns pretending to regulate the industry.
Normally something like this should have been proposed by a major like Pfizer as one of their many blockbuster billion dollar drugs, but instead a relatively small company is offering it for only $50K/yr per victim of taxpayer medicare money.
Essentially the wrong people are making money so the insider kingmaker types are PISSED off.
Now if the regulators were made up of people trying to have a career at Biogen then the regulators would be happy to approve this billion dollar blockbuster. But instead they're Pfizer (and other) career minded people so they're pissed.
In the end it'll be something like pfizer buys biogen for $20B instead of $10B and the price of the drug will be boosted up another $10K/yr per victim to pay for all the financial foolishness. Kinda like how endless mergers in the phone company arena changed the industry from $5 for a legacy POTS line to $50.
(Score: 1) by js290 on Friday June 11 2021, @08:00PM
(Score: 1, Informative) by Anonymous Coward on Friday June 11 2021, @11:36PM
There are a couple of issues here. First is that AD research has fundamental problem with noisy data. An individual with AD does not show slow and steady cognitive decline. They can jump up and down; they can stay steady and then show steep decline; they can improve apropos of nothing. This makes comparing groups notoriously difficult. There very well could be an improvement here, but is hidden in the noise, or their could be nothing and the trial showing great success was a type I error.
Another issue is that AD might actually be a family of diseases with different but related causes. There are a number of genetic sources of early-onset AD, most of which directly alter the production of amyloid beta and its interactions. The cause of AD in those situations is the amyloid beta's effects, whether directly or indirectly. Another poster mentioned the cholinergic hypothesis, but that has problems because not everyone responds to that class of drugs, especially in genetically-caused individuals, and AD progression continues, which suggests that acetylcholine may be an indirect cause/effect of AD or the trigger of a subset of the disease proper. There is also inflammation, autoimmune, tau, metabolic, and other hypothesis, but most of them are in the form of a trigger that then causes numerous side effects, including amyloid beta effects, which then progress into full-blown AD. Together this all suggests that AD is multiple disease states that eventually converge onto what most people consider AD proper. The problem in telling them apart is, again, that AD research is notoriously noisy.