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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?

#151

Post by mft_ »

StableAlkyne wrote: post #111
londons_explore wrote: post #101

Earlier quoted context omitted.

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 harde…

The struggle is the high level regulatory bodies (with the exception of aberrations such as the current admin's approach to appointment) generally select for individuals with a low risk tolerance. Low risk tolerance is generally incompatible with speed - it's a miracle the covid vax and treatments were approved as quickly as they were in 2020. Biggest example of this risk aversion is the peptide craze going on (the m…

> The struggle is the high level regulatory bodies (with the exception of aberrations such as the current admin's approach to appointment) generally select for individuals with a low risk tolerance.

This may be true, but I don't think it's the major driver of conservatism. Two thoughts/observations:

1) Bodies like the FDA face a strongly skewed set of incentives. If they take a risk on something and people get hurt, they face huge public criticism. If they take a risk on something and it's all fine, very few people care or notice. As such, they are strongly driven to not make a public mistake - which drives ever more conservatism.

2) FDA can actually be innovative compared to other health authorities. Breakthrough therapy designation, Project Optimus, Project Frontrunner, and others - show this. However, they've got a strong 'not invented here' mindset - they flatly refuse well-meaning individual innovations from pharma companies, if they're not compatible with FDA's guidelines. And they're heavily bureaucratic, meaning the innovations that do appear are usually following years of process (which probably links back to #1).

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

#152

Post by dannyw »

hn_throwaway_99 wrote: post #90

I'm surprised there was no mention (at least none that I found when searching) of the relatively recent research coming out of Harvard regarding the hypothesis that low levels of lithium in the brain are responsible for a lot of Alzheimer's cases. The research is still in the very early stages (largely mouse models, though they did develop the hypothesis by looking at differences in human brain tissue post mortem), b…

I agree with your post and the well-studied safety of it in humans at appropriate doses :) but the study you linked is on rats; and so there’s probably another better study to link.

I experiment and take a small number of less-commonly-known supplements and those kind of studies _in itself_ should never contribute to “it’s safe for humans”.

Anecdata: my personal brain/body didn’t react too well to 1mg a day, I felt somewhat ‘sluggish’ and found concentrating harder, so I stopped after 2 days out of being conservative. Perhaps I’d get used to it, but for me personally, I was surprised at the effects of just 1mg so I didn’t want to continue taking it.

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

#153

Post by enraged_camel »

bradley13 wrote: post #145
gruez wrote: post #35

Earlier quoted context omitted.

> 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...

Pretty clearly not. It would seem that beta amyloids correlate with Alzheimer's, but do not cause it. The problem us "consensus science". You could get funding to research beta amyloids, but not to research any competing hypotheses. It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.

>> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.

Nonsense. It is actually quite unlike climate science, where the consensus of catastrophe and the evidence for it are both overwhelming. Dissenters are listened to only to the extent they can provide overwhelming evidence to the contrary, which they so far cannot.

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

#154

Post by ArnoldusManlius »

What are the 3 pro’s of Alzheimer’s disease? The 3 pro’s of Alzheimer’s disease are: - Every day you make new friends - You can hide your own eastern eggs - And every day you make new friends ——- This a a bit of a dark joke that goes around in The Netherlands. In Dutch it goes like this: Wat zijn de drie voordelen van Alzheimer? De drie voordelen van Alzheimer zijn: - je maakt elke dag weer nieuwe vrienden - je kan je eigen paaseieren verstoppen - en je maakt elke dag weer nieuwe vrienden —- The meaning of this joke is not to ridicule patients whom suffer from Alzheimer’s disease. Not at all. It is just meant to make people smile for just an instant. And making them experience a little how Alzheimer’s can affect your brain.

About the question: Alzheimer’s disease is a condition of the elderly, and they’re on their way out anyway. That is what I observe. Healthcare is a moneymaking business. In capitalism. While it should be free. And excluded from patenting or copyrighting. Healthcare has turned into wealthcare. No wealth? Game over. No extra life for you. On the other hand, maybe the subject is just so complicated for today’s scientists. It is all in the eye of the beholder. The existence of F1 racing cars doesn’t mean that Tesla will never be part of Formula One’s future. As we speak there’s already one Tesla racing through space…

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

#155

Post by less_less »

verisimi wrote: post #110
dvfjsdhgfv wrote: post #95

Earlier quoted context omitted.

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, a…

I've hung out with a lot of pharma folks, and the business is really complicated. Most of the companies aim to both help people and to make a lot of money, and will choose projects based on some balance of those -- sometimes in dubiously ethical ways (e.g. tweaking formulations of existing products to extend the patent) and sometimes in basically fine ways (e.g. lots of the improvements in diabetes management which have helped a ton of people; at least the targeting is fine here though often not the pricing). Obviously chronic diseases that affect lots of rich people are a prime target to make money, so drug companies make lots of drugs for these, and they usually aren't curative because chronic diseases are hard to cure (but see e.g. Hep C which is now curable). There are also companies with rich investors who want to cure death, or at least cure particular diseases that they fear or have a genetic predisposition to (lots of unethical behavior from a certain now-defunct company that tried to do this).

For cancer in particular, pharmas don't (and mostly can't) just target a drug to chronically treat some cancer over the long term but not cure it. Instead they pick some target that's believed to contribute to development (/ metastasis / treatment resistance / whatever) in whatever cancer, and make a drug to interfere with it or to target an immune response to cells that make it. If it's stable, nontoxic, and looks potentially effective enough they'll take it to clinical trials. During clinical trials they'll find out whether it does nothing, gives you a few extra months, or has a chance at curing the disease. Usually the answer is that it does nothing or almost nothing, or isn't worth the side effects, and then the company wasted its time and money. Drugs with a chance to cure common types of cancer can be enormous successes -- see eg Herceptin.

Cancers are difficult diseases and it's rare to find something that reliably cures them. But drug companies aren't pulling their punches. Like they would never say "oh this drug clears breast cancer too reliably, we should make it less effective so that people will be more likely to die but also might take it for longer".

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

#156

Post by atombender »

altairprime wrote: post #72

Now that the “plaques are the disease” folks are having to listen to viable research in contradiction to them, there is a possible outcome that an mRNA vaccine for tooth decay ais also an mRNA vaccine for Alzheimer’s, if that particular theory pans out. Which would subtract a trillion dollars from GDP over a medium timescale. I remain hopeful :) but I’m not particularly holding my breath for the U.S. to invent a cure…

Do you have a link? A biotech company called Cortexyme already tried a drug against P. gingivalis, which causes gum disease, based on the idea that these bacteria migrate to the brain (many old people who died of AD have gum disease and tooth loss). But that drug failed phase II/III as there was no evidence of any effect.

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

#157

Post by plqbfbv »

SomaticPirate wrote: post #109
dvfjsdhgfv wrote: post #95

Earlier quoted context omitted.

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. A…

> Part of the reason it is so valuable is that patients usually must take it for the rest of their lives.

Well yes, Ozempic doesn't solve the habits of a bad diet.

The weight rebound is surely due in little part to removal of hunger suppression as in "hormone rebound", but if you resume eating 5000+ kcal/day because you don't have something that keeps you from doing it, you'll end up in the same situation as before. Ozempic was never meant and is not going to fix your diet. That's a psychological and environmental problem.

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

#158

Post by stingraycharles »

bradley13 wrote: post #145
gruez wrote: post #35

Earlier quoted context omitted.

> 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...

Pretty clearly not. It would seem that beta amyloids correlate with Alzheimer's, but do not cause it. The problem us "consensus science". You could get funding to research beta amyloids, but not to research any competing hypotheses. It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.

> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.

I think this is not a great example, as there’s a huge group of people that, in fact, does not agree with the consensus and would happily fund research that (tries to) prove otherwise.

I fully agree with your point, though, just not the example.

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

#159

Post by pcrh »

Unable to read the full article, however the amyloid hypothesis is not without solid scientific foundations.

Alzheimer's disease may occur either due to inherited mutations in the genes for APP or presenilin, in which case it can occur as young as 40 yrs old. Or it may occur "sporadically" in those over 65yrs old. The brain pathology of both is similar. Notably, amyloid is derived from APP in part by the action of presenilin, which cuts the APP protein to release the amyloid peptide (Aβ).

Currently, the amyloid hypothesis is the only known way to reconcile the similarity of pathology (for both amyloid and tau) between early onset inherited AD caused by mutations in either APP or presenilin, and later onset sporadic disease. Furthermore, all the mutations in APP that cause Alzheimer's disease are located within or adjacent to the region that corresponds to Aβ amyloid, and not in the remaining 95% of the molecule.

Until another way of unifying these observations is found, the amyloid hypothesis will always find supporters.

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

#160

Post by Noaidi »

I would people need to read the #1 post on HN today to get a clue why they are failing with Alzheimer's.

https://www.scientificamerican.com/article/amateur-armed-wit...

Just like that math problem, we are starting off with wrong thinking right from the beginning. Some researchers are already talking about this but the plaques are actually a protective response to a metabolic problem in the brain which has to do with glucose transport.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8772148/

This is why people with dementia and Alzheimer's crave sweets so much:

https://helpdementia.com/why-dementia-patients-crave-sweets-...

Alzheimer's is not a neurological problem, it is a metabolic problem.

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