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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?

#101

Post by londons_explore »

cpgxiii wrote: post #67
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 po…

I would like to see the FDA get rid of their binary "Approved" approach.

Instead, at the start of a treatment on a patient, an analysis must be done of all available data, and the treatment only allowed if the error bars put it within the realm of the best treatment available.

That means at the start when not much data is available, it is easy to give it to a patient. But over time as more data comes in it gets harder and harder to do so if the treatment is ineffective or harmful.

Data should be collected and analyzed in real-time - it should be a matter of hours between some life event like a death feeding into the dataset used for decisions on new patients.

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

#102

Post by Maxion »

panabee wrote: post #28
manquer wrote: post #20

Earlier quoted context omitted.

> gatekeepers directly or indirectly control research funding. Perhaps funding like public grants could be controlled by few? Should not the case for private money? Relatively common health issues older people tend to get fair amount of private funding after all. Rich people tend to be older and they are lot more likely to see amongst their friends and family Alzheimer's and Parkison's or even cancer and so forth and…

If you're a wealthy person lacking a neurobiology background, how do you decide which research efforts are the most promising? Which labs do you back? Generally, you rely on experts. Who typically became experts by adhering to the conventional wisdom set by gatekeepers. "Science advances one funeral at a time" feels apt. Sadly, the problem isn't confined to Alzheimer's. Whenever only a few people decide what is "righ…

What also happens is these gatekeepers end up being those requested to review papers. When a paper comes up for review that challenges the status quo these gatekeepers nit-pick the paper and recommend it not be published. This happened to my wife on numerous occasions. She has a few unpublished papers because of this. What she found in her research has since become the common accepted knowledge in her field after a few funerals.

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

#103

Post by tsoukase »

It's because there is little progress in uncovering the mechanisms of the disease. Alzheimer's et al are tau-opathies and Parkinson's et al are synuclein-opathies. Both are degenerative and we wait for their common base in a Grand Unified Theory.

I like to view degeneration of any tissue as death due to (premature) aging. So, if we treat it, we achieve immortality by applying it to all body. This is something hard.

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

#104

Post by ddorian43 »

adi4213 wrote: post #75

The company I work at has been building a dementia prevention program covered by most insurance plans in the US. Our clinicians work directly on helping understand risk of neurodegenerative disease and help tailor personalized plans to improve outcomes. A recent lancet study concluded that around 45% of dementia cases are preventable [0] Happy to answer any questions people have. https://www.betterbrain.com Disclaime…

What is your approach towards nutrition ? Meaning which exact diet do you expect to help in mental health?

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

#105

Post by Closi »

dvfjsdhgfv wrote: post #95
verisimi wrote: post #85

Earlier quoted context omitted.

> Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. To be clearer, Pharma is chasing a nice long treatment plan, that will require expensive drugs till the end. Pharma does not heal - this is not good for business. So there are criteria around what they are searching for.

I think you are wrong, for several reasons. From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole). From marketing and sales perspective, look at what happen to pharma companies capitalization when Ozempic appeared: a relatively small El…

Plus even if it does involve expensive drugs and long term treatment, that would be a huge step towards cheap drugs and short term treatment.

Lots of treatments start expensive and then come down in cost as competitors step in.

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

#106

Post by RagnarD »

Because of almost certainly fraudulent science. See https://www.science.org/content/article/potential-fabricatio.... Research was misled for decades down the path of assuming that Amyloid plaques are causative of Alzheimers, a now disproven theory (there's an association, but that's not the same as causative.)

Scientist Ruth Itzhaki spent years studying a far more promising theory of Alzheimer's: that it's caused by viral infection in the brain, particularly HSV-1, best known for causing cold sores. Most have it, so there are clearly other factors at work, likely related to susceptibility in particular individuals to to the virus infecting the brain and spreading over time. See https://pubmed.ncbi.nlm.nih.gov/34205498/

The implication is that anti-viral treatments are likely to inhibit and potentially cure Alzheimer's. There is already unintended evidence along these lines, both via antiviral drugs and vaccines.

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

#107

Post by Mistletoe »

mongol wrote: post #97
Mistletoe wrote: post #96

Earlier quoted context omitted.

Every time I read about it and get jazzed I take it and feel awful. I’m guessing my brain chemistry is better without it.

Awful how?

My spreadsheet says it makes me feel incredibly sleepy.

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

#108

Post by Drupon »

gruez wrote: post #35
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…

> Problem was, the model was wrong. I thought despite the fraud, it's still the best model we have[1]? The fact there was fraud doesn't mean the model is immediately incorrect. At best, it means its foundations are shakier than we thought, but it's not a slam dunk repudiation. [1] https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...

>I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field

If anyone wants to know who wrote the article linked before wasting time reading it, there you go.

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

#109

Post by SomaticPirate »

dvfjsdhgfv wrote: post #95
verisimi wrote: post #85

Earlier quoted context omitted.

> Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. To be clearer, Pharma is chasing a nice long treatment plan, that will require expensive drugs till the end. Pharma does not heal - this is not good for business. So there are criteria around what they are searching for.

I think you are wrong, for several reasons. From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole). From marketing and sales perspective, look at what happen to pharma companies capitalization when Ozempic appeared: a relatively small El…

I agree with you but Ozempic is a bad example here. Part of the reason it is so valuable is that patients usually must take it for the rest of their lives. Its actually the perfect example of “evil” pharma since patients slmost akways regain the weight if they stop taking it. This leads to dependence or people searching for grey market sources.

An example of “good” pharma would be Hepatitis C. We can now cure that. Although, pharma is charging the lifetime equivalent in order to do that (a treatment can run over $100k and insurance balks at covering it)

So pharma will absolutely develop a cure if they can. They however will still charge you as if you had to take a dose for the rest of your life.

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

#110

Post by verisimi »

dvfjsdhgfv wrote: post #95
verisimi wrote: post #85

Earlier quoted context omitted.

> Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. To be clearer, Pharma is chasing a nice long treatment plan, that will require expensive drugs till the end. Pharma does not heal - this is not good for business. So there are criteria around what they are searching for.

I think you are wrong, for several reasons. From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole). From marketing and sales perspective, look at what happen to pharma companies capitalization when Ozempic appeared: a relatively small El…

Which illnesses have been cured? Diabetes, cancer?

> From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole).

Researchers are people, but they are paid and directed. They can't go off and do what they like. The corporation directs them, and they are paid for their efforts. Researchers (and all working people) aren't doing what is right - they are doing what they are paid to do.

All the financial upside for pharmaceuticals is in prolonged treatments. It is a 'long sickness' industry. This is perhaps too bitter a pill to swallow for most, so this is where marketing and education come in with the sugar.

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