8 ms·

> Over 56 days, the treatment reduced toxic amyloid-beta by 42 per cent and improved spatial learning by nearly 44 per cent So there's some benefit. Sounds li

> Over 56 days, the treatment reduced toxic amyloid-beta by 42 per cent and improved spatial learning by nearly 44 per cent So there's some benefit. Sounds like their next step is a much larger trial to answer the question you are posing.

mimicmagnet 3mo ago
https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252 https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252 In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.
- bluGill 3mo ago
  It is a repeating trend in all medical research. However enough does turn out to work in humans that we eventually make useful progress.
  - wk_end 3mo ago
    In general, sure, but in this specific instance (treating Alzheimer's by clearing amyloid-beta) it's been shown over and over again to not work in humans.
    - russfink 3mo ago
      I’m kinda new to this - so what you’re saying is the mouse model induces beta-amyliods directly, rather than finding ways to give mice Alzheimer’s, whereas the human tests are for humans that have Alzheimer’s? Meaning we aren’t doing any tests of simply stimulating BA growth in humans?
      - wk_end 3mo ago
        I'm also not exactly on expert on this myself, take it with a grain of salt, but my understanding is that we don't really know what Alzheimer's is. To our knowledge there isn't a clear physical cause we can point to - a virus or bacteria or tumor or something. We have the symptoms, and we have the observation that Alzheimer's patients have amyloid plaques in their brain - among other differences! Since mice don't ever get Alzheimer's naturally, and we don't actually know what Alzheimer's is, we don't know what it would even mean to give mice Alzheimer's. But for research we've genetically engineered mice that end up with lots of those plaques, and their behaviour does suggest an impairment similar to Alzheimer's, so that's what we've been working with. And in those models, various treatments that involve clearing the plaques does seem to help resolve that impairment - but they don't help humans with Alzheimer's, even if they do clear the plaques there too. If I'm reading your question correctly, we can't stimulate amyloid plaque growth in humans for experimentation because that'd almost certainly be considered completely unethical. And also our methods for inducing the amyloid plaques involve mice that are genetically modified from birth rather than something we introduce in vivo, which would somehow be even more unethical than experimenting on live humans. It's possible we could make those genetic modifications in vivo now with recent developments in gene therapy, but...why?
    - XorNot 3mo ago
      Which is not the point of the research paper: the point of it is they've targeted a novel mechanism (waste clearing) and observed two effects impacting markers for Alzheimer's. Amyloid beta might not be causative, but if you hit a mechanism then it stands to reason it might be indicative - in this case if Alzheimer's is partly or fully caused by a waste removal problem in the brain.
TaupeRanger 3mo ago
The word "benefit" does not apply here. The only "benefits" patients and families care about are: 1) does the patient live longer, and/or 2) does the quality of life improve in a meaningful way? Amyloid plaques are a surrogate marker, and (as already explained by many people in this thread) have not been established as a causal factor in disease. In fact, some work has even suggested a protective role for plaques. So we do not have enough evidence to say that a 42% reduction in amyloid-beta IN MICE relays any benefit at all to humans. You are correct that a series of clinical trials, which would take 7-10 years, would clear things up. But for now, we simply don't know.
- Erem 3mo ago
  > improved spatial learning by nearly 44 per cent We care about this part

mimicmagnet 3mo ago

https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252 https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252 In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.

bluGill 3mo ago
It is a repeating trend in all medical research. However enough does turn out to work in humans that we eventually make useful progress.
- wk_end 3mo ago
  In general, sure, but in this specific instance (treating Alzheimer's by clearing amyloid-beta) it's been shown over and over again to not work in humans.
  - russfink 3mo ago
    I’m kinda new to this - so what you’re saying is the mouse model induces beta-amyliods directly, rather than finding ways to give mice Alzheimer’s, whereas the human tests are for humans that have Alzheimer’s? Meaning we aren’t doing any tests of simply stimulating BA growth in humans?
    - wk_end 3mo ago
      I'm also not exactly on expert on this myself, take it with a grain of salt, but my understanding is that we don't really know what Alzheimer's is. To our knowledge there isn't a clear physical cause we can point to - a virus or bacteria or tumor or something. We have the symptoms, and we have the observation that Alzheimer's patients have amyloid plaques in their brain - among other differences! Since mice don't ever get Alzheimer's naturally, and we don't actually know what Alzheimer's is, we don't know what it would even mean to give mice Alzheimer's. But for research we've genetically engineered mice that end up with lots of those plaques, and their behaviour does suggest an impairment similar to Alzheimer's, so that's what we've been working with. And in those models, various treatments that involve clearing the plaques does seem to help resolve that impairment - but they don't help humans with Alzheimer's, even if they do clear the plaques there too. If I'm reading your question correctly, we can't stimulate amyloid plaque growth in humans for experimentation because that'd almost certainly be considered completely unethical. And also our methods for inducing the amyloid plaques involve mice that are genetically modified from birth rather than something we introduce in vivo, which would somehow be even more unethical than experimenting on live humans. It's possible we could make those genetic modifications in vivo now with recent developments in gene therapy, but...why?
  - XorNot 3mo ago
    Which is not the point of the research paper: the point of it is they've targeted a novel mechanism (waste clearing) and observed two effects impacting markers for Alzheimer's. Amyloid beta might not be causative, but if you hit a mechanism then it stands to reason it might be indicative - in this case if Alzheimer's is partly or fully caused by a waste removal problem in the brain.

TaupeRanger 3mo ago

The word "benefit" does not apply here. The only "benefits" patients and families care about are: 1) does the patient live longer, and/or 2) does the quality of life improve in a meaningful way? Amyloid plaques are a surrogate marker, and (as already explained by many people in this thread) have not been established as a causal factor in disease. In fact, some work has even suggested a protective role for plaques. So we do not have enough evidence to say that a 42% reduction in amyloid-beta IN MICE relays any benefit at all to humans. You are correct that a series of clinical trials, which would take 7-10 years, would clear things up. But for now, we simply don't know.

Erem 3mo ago
> improved spatial learning by nearly 44 per cent We care about this part