This has been demonstrated for many years. And yet we waste literally billions per year researching treatments that will only work in mice. And yet we regularly publish articles proclaiming that we can cure mice, humans are next!
This research is BS and a waste of taxpayer money.
Every step of the way towards the resolution of the issue is important. Even ruling out what does not work is important.
Without those incremental advancements, we may never reach the end goal.
But sometimes the lesson to be learned is that what we were is a bad approach, and we need to rethink things. We can't simply run experiments and get results. We also need to study whether our experiments are telling us what we think that they are telling us. Because if we don't know what our experiments are actually telling us, we're going to misunderstand the results.
https://people.cs.uchicago.edu/~ravenben/cargocult.html is worth a read on this. Among other examples, it includes an explanation of what actually has to be done in order for a rat running a maze to actually test the rat's memory. And how it is that we know that this is what has to be done.
The fact that psychologists ignored that experimental procedure marked psychology as a cargo cult science. (Some 40 years later, the replication crisis forced psychologists to at least talk about the issues that Feynman raised...)
The fact that we continue testing animal models of Alzheimer's that we have proven to be a bad model of humans, likewise shows that Alzheimer's research has become a cargo cult science.
Partially. It also, more primarily, shows that medical funders and ethics committees demand very strong evidence in one animal model before they allow you to move a step "up the ladder" towards humans. What you can test on mice, you haven't managed to get approval to test in nonhuman primates. What you can test in nonhuman primates, you might get approval to test in humans. What you can test in humans, might finally prove useful for treating humans.
But the broad assumption is that if something fails in mice, we can know it would have been unethical to try it on humans first.
Somebody else asked "what is your alternative?" and you responded with "drunk under a streetlamp". The issue with this is that all of science is drunks under streetlamps. Scientists rely on a set of methods; for preclinical work, this is animal models, organoids/tissue chips (still in development), and in-silico AI stuff. Slim pickings! To use your lamp analogy, all of these options will give off a pretty dim amount of light.
Our working theory is that amyloid beta plaques cause Alzheimer's, and so preventing them will prevent the disease. We have absolutely demonstrated our ability to prevent those plaques in both mouse models and humans. Doing this cures symptoms in mouse models. It does not cure symptoms in humans. I already gave a list of 9 different approaches that generated this exact result. How many more billions do we need to spend on new approaches to do the same thing, before the field reconsiders the theory?
And the failure here is not just with failed drug trials. In this century, it is easier to find fraudulent data advancing the hypothesis, than real data. With the result that several fraudsters have managed to create very good careers for themselves before being caught. This is a sign that there is something very deeply wrong with the field, if such fraud is rewarded rather than being caught more promptly.
Furthermore you are absolutely wrong about what I said about the alternative. My drunk under a streetlamp comment was about continuing to use these animal models to create more drugs. My suggested alternative was basic science. If amyloid beta plaques are a symptom, not a cause, of Alzheimer's, then what is the cause? We need to figure that out, before trying to create new drugs for it.
And it isn't like basic research has nothing to try. Alternate hypotheses with some suggestive data for them include Tau folding, inflammation (possibly caused by viruses), problems with the blood-brain barrier, problems with the mitochondria of neurons, dysregulation of metal ions, and so on. Maybe the real answer is not even on this list. But finding and demonstrating the real cause should be a high priority.
My father-in-law has Alzheimer's. If research continues for the next 30 years like it has in the last 30 years, there will still be no treatment when my wife gets old enough to worry about getting it. This is not a potential future that I'm particularly looking forward to. (But maybe I'll get lucky and get it before her...)
Isn't that what the animal experiments are for? Trying to find causation?
The fact it has to be done with mice is the best we can do. The article also does not elaborate on what interesting modeling or synthesis techniques might have been used, which could be more generally applicable.
The models have worked often enough that it is reasonable to hope that what works in animals, will work in humans. And it is easier to experiment on animals. This is why they are used in research.
But when what works in animals doesn't work in humans, repeatedly, we should stop using that animal model in research.
Here are examples of treatments for Alzheimer's that worked in animals, reached human trials, then failed to help humans: AN1792 (active Aβ vaccine, Elan), Tarenflurbil (R-flurbiprofen), Semagacestat (γ-secretase inhibitor), Bapineuzumab (anti-Aβ mAb), Solanezumab (anti-Aβ mAb), Crenezumab, ponezumab, gantenerumab, and BACE inhibitors (e.g. verubecestat, atabecestat).
All of these were considered promising enough in mice to be worth expensive human trials. Where they failed. Those weren't cheap failures, either.
https://grants.nih.gov/news-events/nih-extramural-nexus-news...
At this point it is a waste of time and money to produce more drugs that are guaranteed to fail in humans. Making it harder to waste time and money in this way is a feature, not a bug.
After we have better basic science about what likely causes Alzheimer's, we can go back to the question of how to find drugs that might help. Trying to do it in the other order is putting the cart before the horse.
Sincere question: wouldn’t the great energy and intensity you’re putting into web forum replies be better channeled into Alzheimer’s advocacy?
We have to make do with the tools available to us.
Mice have absolutely dominated research because they're relatively cheap, lots of powerful genetic tools are available, and the PR is more tractable. However, that doesn't mean they're the right choice for every experiment.
(Sorry, this is a rude joke. Truthfully my disagreement with patent is only medium-strength. I just can’t resist jokes.)
Did you have a substantive response? Or are you just here to deliver meaningless snark?
But in case it isn't clear: All models are inherently imperfect. That doesn't mean they aren't useful. The ideal test subject tends to complain when you propose dissecting their brain for analysis.
Instead I will trust that those in the audience that I might care about, can judge your lies and insults correctly.
Right?
Though I would say that creating a pseudo-human brain in a vat and giving it Alzheimers would be pretty controversial.
"we waste literally billions per year researching treatments"
Sir, do you realize that in science, you principially DON'T KNOW IN ADVANCE WHAT WILL WORK AND WHAT WON'T?
Yes, we could experiment on primates instead, but in that case, be prepared to shell maybe thirty times as much money for the same research. Mice are cheap. Monkeys are not.