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Why has there been so little progress on Alzheimer's disease?

freakonomics.com

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Re: Why has there been so little progress on Alzheimer's disease?

#61

Post by anon84873628 »

cookiengineer wrote: post #44

...because Alzheimer is a dormant side effect of a virus, not of a messenger chemical. But that doesn't go well in studies and "self populism" of what funded research wanted to hear. If you study effects and not causes due to lack of measurements for reproducibility in any field of research, that's what comes out. Also check out how the new and promising correlation started by observing the Wales eligibility for mand…

Gee, that sure is a confident statement of fact.

Or maybe virus activity is one way that a negative feedback loop involving protein aggregates can begin...

Re: Why has there been so little progress on Alzheimer's disease?

#62

Post by ramraj07 »

jleyank wrote: post #30

They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most gues…

[flagged]

Re: Why has there been so little progress on Alzheimer's disease?

#63

Post by ramraj07 »

bsder wrote: post #40
jleyank wrote: post #30

They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most gues…

The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis . What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza…

There were no cointerarguments? There was a very simple counterargument: where was the causal data? If none exist why should I counter argue when you hadn't proven it to begin with.

Re: Why has there been so little progress on Alzheimer's disease?

#64

Post by chiefalchemist »

robwwilliams wrote: post #2

The major problem has been lock-in of the Abeta 42 peptide fragment as the cause. This monomaniacal focus was rewarded by grant awards to team players. Karl Herrup has a terrific book on the topic How Not to Study a Disease — The Story of Alzheimer’s from MIT Press (2021, ISBN 9780262045902). He did not win many friends but I think he is right. The consensus now is that many factors contribute to the heterogeneous di…

There’s another book mentioned in the podcast called “Doctored.” The gist is: bogus “science” led to loads of money / research going in a direction that was effectively fiction.

People love to praise “the science” when they mean the scientific method. What they always seem to forget is that method is executed by humans. Imperfect, sometimes ego driven humans.

Re: Why has there been so little progress on Alzheimer's disease?

#65

Post by bsder »

ramraj07 wrote: post #63
bsder wrote: post #40

Earlier quoted context omitted.

The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis . What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza…

There were no cointerarguments? There was a very simple counterargument: where was the causal data? If none exist why should I counter argue when you hadn't proven it to begin with.

There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others.

The hypothesis didn't come from nowhere.

To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effect.

Re: Why has there been so little progress on Alzheimer's disease?

#66

Post by ks2048 »

It's good to expose fraud and it does sound like this set back the field, but "Why has there been so little progress"? - probably because it's very hard? We barely understand how the brain stores memories.

I'm dealing with someone with this disease now and it's absolutely hell.

Re: Why has there been so little progress on Alzheimer's disease?

#67

Post by cpgxiii »

mehrshad wrote: post #42

https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte... "Despite being described as a “cabal,” the amyloid camp was neither organized nor nefarious. Those who championed the amyloid hypothesis truly believed it, and thought that focusing money and attention on it rather than competing ideas was the surest way to an effective drug. It has not worked out that way. Research focused on amyloid, and the developmen…

> The FDA's approval process is stymied by a CYA culture that fails to adopt the risk profile it needs to in order to potentially save large contingents of sick and dying.

Except the history of FDA approval here is that it has been too accepting of drug candidates for Alzheimers with very weak evidence of efficacy and serious side effects. This particular field would probably be better off if the FDA took a harder position on efficacy, rather than deferring to drug companies and patient/caregiver groups that desperately want something.

Re: Why has there been so little progress on Alzheimer's disease?

#68

Post by IanGallacher »

PaulKeeble wrote: post #5

Its done substantially better than more common diseases like ME/CFS which very few have even heard of let alone know the symptoms of and receives almost no funding at all. Alzheimer's received a further $100 million of NIH funding earlier this year ( https://www.alz.org/news/2026/100-million-dollar-alzheimers-... ). That is 6 times the total funding for ME/CFS federally which is currently just 15 million and planned…

It is a crime and a tragedy how criminally underfunded ME/CFS is.

I'll probably be downvoted for this, but I honestly think quality of life of CFS is lower than Alzheimer's.

I truly wish that disease funding was based on science and metrics rather than marketing and vibes.

That being said, Alzheimer's absolutely deserves it's funding and it is very sad to see setbacks related to fraud.

Re: Why has there been so little progress on Alzheimer's disease?

#69

Post by nickburns »

anon84873628 wrote: post #61
cookiengineer wrote: post #44

...because Alzheimer is a dormant side effect of a virus, not of a messenger chemical. But that doesn't go well in studies and "self populism" of what funded research wanted to hear. If you study effects and not causes due to lack of measurements for reproducibility in any field of research, that's what comes out. Also check out how the new and promising correlation started by observing the Wales eligibility for mand…

Gee, that sure is a confident statement of fact. Or maybe virus activity is one way that a negative feedback loop involving protein aggregates can begin ...

Sure is a line of inquiry worth pursuing either way, no?

Re: Why has there been so little progress on Alzheimer's disease?

#70

Post by pabs3 »

notepad0x90 wrote: post #53

I'll say that I know nothing about this, but just commenting on the economics of it all: Cancer and HIV have been at the forefront of disease research, in terms of public interest and financial investment, and cancer is more like an umbrella of similar diseases than a single disorder. HIV is manageable these days, and cancer research is slowly seeing leaps in progress. Alzheimer is very important, and affects a very…

> Alzheimers feels like something only old people get

https://en.wikipedia.org/wiki/Early-onset_Alzheimer%27s_dise...

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