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

freakonomics.com

141–150 of 355 posts

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

#141
post #70

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...

> Nonfamilial early-onset AD can develop in people who are in their 30s or 40s, but this is extremely rare, and mostly people in their 50s or early 60s are affected.

Depending on what you consider "old", this might not change much

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

#142
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…

> 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.

> 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.

This is a trope regurgitated by people who don't know any better. It would imply that pharma are deliberately avoiding research directions that would generate cures, or (even worse) discovering cures and putting them in a dark secret safe somewhere.

The reality is that drug development is serendipitous and really hard, and any company seeing even a sniff of a drug that works will throw everything behind making that drug a success. During the early stages of investigation of a promising new agent, the animal data can't predict much, and certainly can't predict whether something is "curative" - this would only be seen during human trials, after which hiding that benefit would be close to impossible. It's just not how it works.

There are plenty of examples of actual (rather than functional) cures being developed and marketed:

1) Previously-untreated DLBCL (a type of blood cancer) can be cured. CHOP chemotherapy cured ~35-40% of cases. The addition of rituximab boosted that to 60-65%. There then followed a long string of failed phase III studies (probably billions spent, cumulatively) trying to beat rituximab + CHOP, and finally in recent years there has been some success. So: multiple attempts across multiple pharma companies, trying to improve on an already impressive cure rate... not much evidence of an anti-cure conspiracy.

2) Hepatitis C - cures were discovered and marketed from ~2014 onwards; now ~95% of cases can be cured with a treatment lasting only a couple of months. So: multiple treatments, from multiple pharma companies, which offer a hugely effective cure for a pretty unpleasant disease.

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

#143
post #112

Earlier quoted context omitted.

there is even easier way to estimate the chances of time wasting - it is a "rationalist" website, an "effective altruism"-like version of rationality. wrt. original post - quickly googled, and that for example https://www.news-medical.net/health/What-are-Amyloid-Plaques... - pretty short and seems to be clear that amyloids do have some correlation while may or may be not the cause. "Amyloid plaques form one of the tw…

Huge codebase with years of fixes, features and hacks added on top and nothing ever refactored. It’s a miracle it works at all

[deleted]

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

#144

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…

> Which illnesses have been cured? Diabetes, cancer?

Type I diabetes - no, but this is a condition in which the body attacks the part of itself that makes insulin. So by the time it happens, it's too late. Sadly, we're generally bad at understanding and preventing autoimmune diseases, but this needs more basic research, not drugs.

Type II diabetes - essentially a lifestyle condition. May be functionally cured in some/many cases with strict lifestyle interventions. Ironically, GLP-1s may help move some people towards a functional cure.

Cancer - yes, where possible. The open secret is that the best way to fight cancer is to not get it in the first place, or failing that to catch it very early, but these are issues of lifestyle and public health policy - both of which we're currently very bad at optimising, as a species.

> All the financial upside for pharmaceuticals is in prolonged treatments.

Except for the examples to the contrary.

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

#145
post #35
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...

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.

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

#146

Earlier quoted context omitted.

Imagine your role is allocating spending on $10B/year of medical research and you are presented with two strategies: spend everything searching for the cure for one poorly understood condition, or allocate to treatments improving standard of care for 100 conditions. Improving standard of care for 100 is less risky/more profitable because you have more shots at an expensive process with a high failure rate. And it is…

I'm genuinely glad you have new treatments and its improving your quality of life. The point I am making is that you are a/ not getting cured, and b/ paying a lot of money. The reason for this, is this is best strategy for maximising profits. Its really the exact same model as your local heroin/crack dealer. Please set me straight if those conditions differ in your case. Profits are what pharma companies want. The co…

The local illicit drug dealer comparison doesn't apply because you can't simply ignore the development time and cost of FDA approved drugs. My post was about allocating limited capital to pharmaceutical research, and maximizing benefit.

Again, if your choice is improving quality of care for 100 conditions or trying to moonshot your way to curing one disease, more patients benefit from the former even if pharma also profits more.

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

#148

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…

It’s actually quite simple: 1–5 mg lithium orotate, vitamin D, omega-3 from algae with high levels of polyphenols, a daily exercise routine, and good food—not the processed crap you often get in the US. My grandmother is 94 and still mentally so sharp that she amazes me every time.

https://michael-nehls.de/

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

#149

Earlier quoted context omitted.

Huge codebase with years of fixes, features and hacks added on top and nothing ever refactored. It’s a miracle it works at all

It is worse. The code changes are mostly random, only surviving the tests of fitness nature is applying (on various levels though; immediately catastrophic changes on level of cell biology are sorted out). And at least the high-level tests are also random and unreliable.

So basically it's a codebase mostly composed of bugs, and the features mysteriously work because they're based on bugs that happen to be mitigated by other bugs. :)

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

#150

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…

I see several people here who appear to be replying to the headline rather than actually reading the article (well, podcast transcript, technically). What you mention is already discussed extensively in the podcast episode, and Matt Shrag (the scientist your first link is about) is the one being interviewed in the podcast.
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