5 ms·

Alzheimer is weird in that plenty of treatment works in mice but fails in humans. I suspect it's primarily because we do not fully understand the cause of Alzhe

Alzheimer is weird in that plenty of treatment works in mice but fails in humans. I suspect it's primarily because we do not fully understand the cause of Alzheimer.

nonbel 8y ago
Why do you think that is weird? My understanding is that "mice studies" cost less than clinical trials, therefore more "mice studies" with (correct/incorrect) conclusions are created.
heyjudy 8y ago
Most likely there is no singular cause, but a slew of contributing factors that prevent amyloid clearance and promote plaque formation. That's why overlapping, holistic solutions like the Bredesen protocol, ketagenic diets and now possibly ultrasound are the best treatment than waiting for a panacea that is unlikely to ever exist.
- bitwize 8y ago
  And don't forget the vipassana and rolfing!
newsbinator 8y ago
Conversely it would be shocking if most things that work on mice worked in the same ways on humans.
- rf15 8y ago
  what are you thinking of specifically? I mean genetically and functionally we are incredibly similar as mammals. Most poisons/etc. work the same for example.
  - zmmmmm 8y ago
    I'm completely speculating, but I think when your lifespan is only 2 years anyway, you have almost no selective pressure for things like the kinds of diseases of aging that humans are now battling. So there are all kinds of things like cancer and dementia that mice's systems are much more naive to, and hence they are tend to get sick from "simple", easily treatable versions of these diseases. Meanwhile humans have evolved strong defenses for all the common / simple causes and are trying to fix the "hard" versions of all these things.
    - ethbro 8y ago
      It's partly because of a more complex version of that, partly because of evolutionary drift. Mammals can still be incredibly distinct when you get down to specific biological pathway behavior. Or they can be exactly the same. Depends on how the mutation dice came up. For example, the different ways various mammal species metabolize theobromine [1] (aka, the "dangerous" thing in chocolate). Dogs and humans are similarly allergic, but because we metabolize it differently it's eliminated from our bodies much more quickly, which keeps it from building up to dangerous levels. As my dad (vet / path / drug development) would say, 'Mother Nature is lazy before anything else. She'd rather repurpose an already evolved system than create something new in almost every circumstance.' Multiply that by ~95 million years (last common dog-human ancestor), and you get a lot of quirky genetic code debt. ;) [1] https://www.ncbi.nlm.nih.gov/m/pubmed/6144479/ https://www.ncbi.nlm.nih.gov/m/pubmed/6144479/
    - mannykannot 8y ago
      There's some evolutionary pressure in the form the selective breeding of animal models of human disease; it just has not been very successful for Alzheimer's. I guess you have to start with what nature gives.
  - dr_dshiv 8y ago
    I saw a lecture recently that sought to compare the difference between mice neurons and human neurons. They were surprised to find that the capacitance of the neural membranes was substantially different. They showed that populations of human neurons we're capable of entraining to frequencies exceeding 1000hz, whereas mouse neural populations capped out below 300hz. I apologize I don't remember the researchers name, but it was at a Human Brain Project conference in Amsterdam.
  - trasz 8y ago
    Out of curiosity, is that property specific to mice, or are most small mammals similar in that regard, and we use mice instead of, say, cats, just because they are more convenient?
JamesBarney 8y ago
This is because our mouse models of Alzheimer disease are terrible. And pretty much everything we've tried has been aimed at beta-amyloid. I think there is a better chance for this therapy because of the way it works, by transition the microglia over to an anti-inflammatory mode. If this procedure passed safety trials I wouldn't be surprised if a similar therapy worked for schizophrenia, anxiety, and depression.
- jf- 8y ago
  I agree that various kinds of immune modulation will be a huge part of medicine in the future. Promising results vs cancer, seems plausible you could teach or program the immune system to attack anything in the body once you’ve identified it. Controlling autoimmunity will also be a challenge.
  - JamesBarney 8y ago
    They've already started doing this with cancer. The problem is the cancer evolves to stop producing the identifiers the immune system was using to determine what to kill.

Alzheimer is weird in that plenty of treatment works in mice but fails in humans. I suspect it's primarily because we do not fully understand the cause of Alzheimer.

nonbel 8y ago

Why do you think that is weird? My understanding is that "mice studies" cost less than clinical trials, therefore more "mice studies" with (correct/incorrect) conclusions are created.

heyjudy 8y ago

Most likely there is no singular cause, but a slew of contributing factors that prevent amyloid clearance and promote plaque formation. That's why overlapping, holistic solutions like the Bredesen protocol, ketagenic diets and now possibly ultrasound are the best treatment than waiting for a panacea that is unlikely to ever exist.

bitwize 8y ago
And don't forget the vipassana and rolfing!

newsbinator 8y ago

Conversely it would be shocking if most things that work on mice worked in the same ways on humans.

rf15 8y ago
what are you thinking of specifically? I mean genetically and functionally we are incredibly similar as mammals. Most poisons/etc. work the same for example.
- zmmmmm 8y ago
  I'm completely speculating, but I think when your lifespan is only 2 years anyway, you have almost no selective pressure for things like the kinds of diseases of aging that humans are now battling. So there are all kinds of things like cancer and dementia that mice's systems are much more naive to, and hence they are tend to get sick from "simple", easily treatable versions of these diseases. Meanwhile humans have evolved strong defenses for all the common / simple causes and are trying to fix the "hard" versions of all these things.
  - ethbro 8y ago
    It's partly because of a more complex version of that, partly because of evolutionary drift. Mammals can still be incredibly distinct when you get down to specific biological pathway behavior. Or they can be exactly the same. Depends on how the mutation dice came up. For example, the different ways various mammal species metabolize theobromine [1] (aka, the "dangerous" thing in chocolate). Dogs and humans are similarly allergic, but because we metabolize it differently it's eliminated from our bodies much more quickly, which keeps it from building up to dangerous levels. As my dad (vet / path / drug development) would say, 'Mother Nature is lazy before anything else. She'd rather repurpose an already evolved system than create something new in almost every circumstance.' Multiply that by ~95 million years (last common dog-human ancestor), and you get a lot of quirky genetic code debt. ;) [1] https://www.ncbi.nlm.nih.gov/m/pubmed/6144479/ https://www.ncbi.nlm.nih.gov/m/pubmed/6144479/
  - mannykannot 8y ago
    There's some evolutionary pressure in the form the selective breeding of animal models of human disease; it just has not been very successful for Alzheimer's. I guess you have to start with what nature gives.
- dr_dshiv 8y ago
  I saw a lecture recently that sought to compare the difference between mice neurons and human neurons. They were surprised to find that the capacitance of the neural membranes was substantially different. They showed that populations of human neurons we're capable of entraining to frequencies exceeding 1000hz, whereas mouse neural populations capped out below 300hz. I apologize I don't remember the researchers name, but it was at a Human Brain Project conference in Amsterdam.
- trasz 8y ago
  Out of curiosity, is that property specific to mice, or are most small mammals similar in that regard, and we use mice instead of, say, cats, just because they are more convenient?

JamesBarney 8y ago

This is because our mouse models of Alzheimer disease are terrible. And pretty much everything we've tried has been aimed at beta-amyloid. I think there is a better chance for this therapy because of the way it works, by transition the microglia over to an anti-inflammatory mode. If this procedure passed safety trials I wouldn't be surprised if a similar therapy worked for schizophrenia, anxiety, and depression.

jf- 8y ago
I agree that various kinds of immune modulation will be a huge part of medicine in the future. Promising results vs cancer, seems plausible you could teach or program the immune system to attack anything in the body once you’ve identified it. Controlling autoimmunity will also be a challenge.
- JamesBarney 8y ago
  They've already started doing this with cancer. The problem is the cancer evolves to stop producing the identifiers the immune system was using to determine what to kill.