7 ms·

What makes me scared about this is that it's immunosuppressive. The immune system is a very important part of the human body, and I worry that taking it could h

What makes me scared about this is that it's immunosuppressive. The immune system is a very important part of the human body, and I worry that taking it could have terrible health impact after years of acting on your body lines of defense. What can you tell me about it?

jonathan-adly 4y ago
Your concern is correct. Suppressing the immune system is a 2-edged sword - a little suppression in the right setting, is extremely beneficial, but go overboard and it is harmful. That's why in a perfect world, we would have large human trials with different dosages and iterate until we can get the maximum benefit and the least harm. The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Also, these kind of trials have to go on for 10+ years at a minimum - which is cost-prohibitive even if it is patentable (not to go in the weeds, but long trials count in the period of exclusivity given to pharma patents). I believe the right approach is to use it off-label, be upfront about the potential risks, and collect lots of data so you can improve as you go. Practical anti-aging so to speak. Another approach is through the NIH grant pathway, but that has a lot of road-blocks as well.
- nico 4y ago
  > The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Same issue with psychedelics. However, they are so useful that people in the medical/therapeutic/academic fields are doing tons of research anyway. Apparently big pharma is also trying to create their own psychedelics (there was an article about it on the front page of HN recently). So far, the business seems like it will be on the assisted therapy side and everything that it entails. So more like services instead of products.
  - trevorishere 4y ago
    SPRAVATO is an example— one of the hands of Ketamine.
- webnrrd2k 4y ago
  Why don't insurance companies fund some of this research? Honestly, I don't know. Wouldn't they want to get treatment costs down? Large HMOs, especially, have motivation to control treatment costs, and access to the patients, data, etc... to make it work.
  - ddingus 4y ago
    Delivering care counts toward their margins, regulated by the ACA. I forget the exact number, but it is 80 percent to be spent on care, something like that. The key thing is more care = more dollars = more in the bank. One response to that legislation was insurers buying care providers.
- sreedhark 4y ago
  I came across this HN discussion, Human Rapamycin Longevity Clinical Trials Begin - https://news.ycombinator.com/item?id=27556564 https://news.ycombinator.com/item?id=27556564 https://www.lifespan.io/campaigns/pearl-participatory-evaluation-of-aging-with-rapamycin-for-longevity/ https://www.lifespan.io/campaigns/pearl-participatory-evalua...
- rewgs 4y ago
  > That's why in a perfect world, we would have large human trials with different dosages and iterate until we can get the maximum benefit and the least harm. Off topic, but whenever I think about this, I find myself thinking that what the world really needs is next-level human/medicinal modeling. Imagine if human trials didn't have to happen in order to know the long-term effects (and in a fraction of the time)!
  - ETH_start 4y ago
    I'm pretty sure AI could do this with enough data.
    - tsol 4y ago
      I'm sure. But it's data we don't even have right now. We don't even know every chemical that naturally occurs in the body, how are we supposed to predict how they could interact with novel chemicals? Some day, though, it may be possible. There was a point where people couldn't imagine these image generation AIs working
      - ETH_start 4y ago
        Yea, data collection is the key here. If we had unobstrusive sensors that people could wear and embed in their body, to continuously measure a multitide of biometrics, that would greatly empower bio-AI systems.
  - giantg2 4y ago
    I'd imagine we'd have to have complete knowledge of the human body to completely replace human testing. There's a hell of a lot that we don't know, especially when it comes to why or how things work.
andy_ppp 4y ago
Is the dose for immune suppression the same effective dose for longevity, i.e. how many mg/kg body weight are we looking at for each thing? It seems pretty safe anyway from my understanding…
adrian_b 4y ago
According to the abstract of the article, its effects, at least in that form of using it, were not immunosuppresive. On the contrary, the protection of the intestine to aging effects was due to increased autophagy in the intestinal cells, which eliminated the defective cells, and by increased levels of antimicrobial lysozyme, and these effects persisted long after the initial treatment ended.
tepitoperrito 4y ago
There's a study on pubmed that suggests it is more immunomodulatory in action than suppressive. I'll update this if I find the link. Edit: it's an opinion article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/
derefr 4y ago
If you think about it, there are specific parts of our immune systems that are likely entirely maladaptive given modern civilization, where people are ~never exposed to parasites, animal venoms, etc. We can turn those parts off, while leaving everything else on, and be better for it (no allergies, psoriatic arthritis, MS, Chron’s, etc.; and so none of the accelerated cellular senescence those conditions provoke in affected tissue.) A lot of recent pharma is already focused on doing specific forms of this at low levels. Every other drug ad in the US is for an immune-receptor blocker of some kind. And the side effects of these drugs come down mostly to the fact that they’re too low-level — they stop these parts of the immune system from being called into action at affected sites, but they leave it active and “patrolling”, such that it attacks harder any tissues that don’t absorb the receptor-blocker well, and such that you get withdrawal effects of potential inflammatory crisis if/when it wears off. Just deactivating the relevant parts of the immune system entirely, on the other hand, provides the same benefits these drugs do, but with none of the “now the rowdy enforcers have nothing better to do, so they go looking for trouble” drawbacks.
- LorenPechtel 4y ago
  Exposure is uncommon, not basically never.
  - giantg2 4y ago
    Exposure to toxoplasmosis is extremely common.
  - derefr 4y ago
    Depends on where you live. For the average human on Earth: sure, merely uncommon. For the average person who lives in a city and rarely goes out into nature, and paranoid-ly avoids doing things like walking barefoot in dung or wearing shortsleeves in forests when they do: effectively never.
    - LorenPechtel 4y ago
      If you live within the malaria zone (and an awful lot of people do) being in a city isn't protection. And the main threat from short sleeves in the forest is things that want your blood, not parasite infection.

jonathan-adly 4y ago

Your concern is correct. Suppressing the immune system is a 2-edged sword - a little suppression in the right setting, is extremely beneficial, but go overboard and it is harmful. That's why in a perfect world, we would have large human trials with different dosages and iterate until we can get the maximum benefit and the least harm. The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Also, these kind of trials have to go on for 10+ years at a minimum - which is cost-prohibitive even if it is patentable (not to go in the weeds, but long trials count in the period of exclusivity given to pharma patents). I believe the right approach is to use it off-label, be upfront about the potential risks, and collect lots of data so you can improve as you go. Practical anti-aging so to speak. Another approach is through the NIH grant pathway, but that has a lot of road-blocks as well.

nico 4y ago
> The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Same issue with psychedelics. However, they are so useful that people in the medical/therapeutic/academic fields are doing tons of research anyway. Apparently big pharma is also trying to create their own psychedelics (there was an article about it on the front page of HN recently). So far, the business seems like it will be on the assisted therapy side and everything that it entails. So more like services instead of products.
- trevorishere 4y ago
  SPRAVATO is an example— one of the hands of Ketamine.
webnrrd2k 4y ago
Why don't insurance companies fund some of this research? Honestly, I don't know. Wouldn't they want to get treatment costs down? Large HMOs, especially, have motivation to control treatment costs, and access to the patients, data, etc... to make it work.
- ddingus 4y ago
  Delivering care counts toward their margins, regulated by the ACA. I forget the exact number, but it is 80 percent to be spent on care, something like that. The key thing is more care = more dollars = more in the bank. One response to that legislation was insurers buying care providers.
sreedhark 4y ago
I came across this HN discussion, Human Rapamycin Longevity Clinical Trials Begin - https://news.ycombinator.com/item?id=27556564 https://news.ycombinator.com/item?id=27556564 https://www.lifespan.io/campaigns/pearl-participatory-evaluation-of-aging-with-rapamycin-for-longevity/ https://www.lifespan.io/campaigns/pearl-participatory-evalua...
rewgs 4y ago
> That's why in a perfect world, we would have large human trials with different dosages and iterate until we can get the maximum benefit and the least harm. Off topic, but whenever I think about this, I find myself thinking that what the world really needs is next-level human/medicinal modeling. Imagine if human trials didn't have to happen in order to know the long-term effects (and in a fraction of the time)!
- ETH_start 4y ago
  I'm pretty sure AI could do this with enough data.
  - tsol 4y ago
    I'm sure. But it's data we don't even have right now. We don't even know every chemical that naturally occurs in the body, how are we supposed to predict how they could interact with novel chemicals? Some day, though, it may be possible. There was a point where people couldn't imagine these image generation AIs working
    - ETH_start 4y ago
      Yea, data collection is the key here. If we had unobstrusive sensors that people could wear and embed in their body, to continuously measure a multitide of biometrics, that would greatly empower bio-AI systems.
- giantg2 4y ago
  I'd imagine we'd have to have complete knowledge of the human body to completely replace human testing. There's a hell of a lot that we don't know, especially when it comes to why or how things work.

andy_ppp 4y ago

Is the dose for immune suppression the same effective dose for longevity, i.e. how many mg/kg body weight are we looking at for each thing? It seems pretty safe anyway from my understanding…

adrian_b 4y ago

According to the abstract of the article, its effects, at least in that form of using it, were not immunosuppresive. On the contrary, the protection of the intestine to aging effects was due to increased autophagy in the intestinal cells, which eliminated the defective cells, and by increased levels of antimicrobial lysozyme, and these effects persisted long after the initial treatment ended.

tepitoperrito 4y ago

There's a study on pubmed that suggests it is more immunomodulatory in action than suppressive. I'll update this if I find the link. Edit: it's an opinion article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

derefr 4y ago

If you think about it, there are specific parts of our immune systems that are likely entirely maladaptive given modern civilization, where people are ~never exposed to parasites, animal venoms, etc. We can turn those parts off, while leaving everything else on, and be better for it (no allergies, psoriatic arthritis, MS, Chron’s, etc.; and so none of the accelerated cellular senescence those conditions provoke in affected tissue.) A lot of recent pharma is already focused on doing specific forms of this at low levels. Every other drug ad in the US is for an immune-receptor blocker of some kind. And the side effects of these drugs come down mostly to the fact that they’re too low-level — they stop these parts of the immune system from being called into action at affected sites, but they leave it active and “patrolling”, such that it attacks harder any tissues that don’t absorb the receptor-blocker well, and such that you get withdrawal effects of potential inflammatory crisis if/when it wears off. Just deactivating the relevant parts of the immune system entirely, on the other hand, provides the same benefits these drugs do, but with none of the “now the rowdy enforcers have nothing better to do, so they go looking for trouble” drawbacks.

LorenPechtel 4y ago
Exposure is uncommon, not basically never.
- giantg2 4y ago
  Exposure to toxoplasmosis is extremely common.
- derefr 4y ago
  Depends on where you live. For the average human on Earth: sure, merely uncommon. For the average person who lives in a city and rarely goes out into nature, and paranoid-ly avoids doing things like walking barefoot in dung or wearing shortsleeves in forests when they do: effectively never.
  - LorenPechtel 4y ago
    If you live within the malaria zone (and an awful lot of people do) being in a city isn't protection. And the main threat from short sleeves in the forest is things that want your blood, not parasite infection.