5 ms·

Fulltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002000 https://journals.plos.org/plosbiology/article?id=10.1371/jou... Summary

Fulltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002000 https://journals.plos.org/plosbiology/article?id=10.1371/jou... Summary: - Inflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is driven to some extent by aryl hydrocarbon receptor (AHR) activation in the gut. - AHR knockout mice are resistant to, or recover more swiftly from, EAE. - An investigation of AHR knockout mice revealed that their microbiomes were different from normal mice in that they produce more bile acids of a certain type, as well as more of certain short-chain fatty acids. - It was hypothesized that these metabolites, which enter circulation generally, alter the disease course of EAE, and affect susceptibility to EAE. - Taurocholic acid, a bile acid that's available as an OTC drug in certain nations, was the most effective AHR-knockout-boosted-metabolite at suppressing EAE, when administered orally. It is suggested as a potential treatment option for MS. - The paper doesn't mention this, but taurocholic acid is hepatotoxic. I believe it remains to be seen whether or not liver-safe bile acids are effective, e.g. tauroursodeoxycholic acid.

drcross 4y ago
>taurocholic acid is hepatotoxic Excuse my rudimentary question but does this mean it would still be possible for administration intravenously?
- Ovah 4y ago
  Nah blood gets filtered through the liver and so would this compounded even if it was intravenously administered.
- A_D_E_P_T 4y ago
  It would still wind up in the liver. In a 1966 paper -- "the metabolism of intravenously injected isotopic cholic acid in Laennec's cirrhosis," by Blum et al. -- it was discovered that "when isotopic cholic acid was administered intravenously to normal subjects, there was a rapid and permanent disappearance of isotope from the systemic plasma, reflecting the essentially complete localization of bile acids in the liver, biliary apparatus, intestinal content, and portal blood." Bile acids might be less toxic if administered via IV infusion, in comparison with oral administration. Then again, they might be more toxic. (Due to rapid excretion or poor absorption via the oral route.) I don't know offhand if one delivery method or the other would be preferred in this regard. But though most bile acids are toxic, not all of them are. TUDCA and UDCA are not only liver-safe, they're first-resort drugs for resolving drug-induced liver damage and promoting liver health. If these "healthy bile acids" can combat MS, that would be a very interesting result. TUDCA and UDCA are very cheap, and their safety profiles are well established.
  - coryrc 4y ago
    From other thread: [the tested drug] taurocholic acid is hepatotoxic You: TUDCA and UDCA are not only liver-safe, they're first-resort drugs for resolving drug-induced liver damage Me: I think I have a stupid idea
- heavyset_go 4y ago
  I have no idea what its metabolic pathways are, but it's possible that by bypassing first pass metabolism might mean that more of the substance reaches the liver versus its metabolites.
citboin 4y ago
tauroursodeoxycholic acid, aka TUDCA. I have M.S. Going to calculate a dose and give it a shot.
- heyoni 4y ago
  Can you share your result?
- nwienert 4y ago
  It's been in study for a wide variety of neurodegenerative diseases, with good early results (ALS is one).
- ramraj07 4y ago
  I sincerely hope you don’t try it without consulting your doctor. EAE mouse models are “like” MS but barely. Something working or not working in EAE models is only a vague suggestion that the same will work or not work on people. This thing can be a supplement but we don’t know how it’ll react with your other medication. The linked article is a fluff piece written by the university PR. According to them every lab in their university is curing cancer and MS and AIDS every day.
  - eyelidlessness 4y ago
    I don’t have MS, but I have friends who do and I fully trust them to be appropriately cautious when they react to relevant medical news. They’re among the most medically informed and adept people I know, and not prone to flights of fancy in MS treatment. Maybe some caution is due in lecturing people about how they address dealing with their own illness.
    - jdwithit 4y ago
      That is wonderful for your friends, but I don't know what they have to do with this individual you have never met. My uncle has lived with MS for almost 50 years and is in the final stages of life unfortunately, which I guess gives me the same level of credibility. I would not advise a stranger on the internet to inject themselves with something based on one study done on mice. I'm also not going to tell them what to do with their own body. But "run it by your doctor first" seems like a reasonable thing to suggest, even if they ultimately decide to do it anyway.
deleted 4y ago
[deleted]
FollowingTheDao 4y ago
> taurocholic acid is hepatotoxic. Taurocholic acid is a huma bile acid. I may increase liver enzyme levels with some patients, but to say it is toxic to the liver is fear mongering. https://www.ncbi.nlm.nih.gov/books/NBK548276/ https://www.ncbi.nlm.nih.gov/books/NBK548276/ Not that I think their research is useful in anyway. Anytime you want to treat a disease through a receptor you always end up with changes in receptor density which make the drug useless. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106030/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106030/

drcross 4y ago

>taurocholic acid is hepatotoxic Excuse my rudimentary question but does this mean it would still be possible for administration intravenously?

Ovah 4y ago
Nah blood gets filtered through the liver and so would this compounded even if it was intravenously administered.
A_D_E_P_T 4y ago
It would still wind up in the liver. In a 1966 paper -- "the metabolism of intravenously injected isotopic cholic acid in Laennec's cirrhosis," by Blum et al. -- it was discovered that "when isotopic cholic acid was administered intravenously to normal subjects, there was a rapid and permanent disappearance of isotope from the systemic plasma, reflecting the essentially complete localization of bile acids in the liver, biliary apparatus, intestinal content, and portal blood." Bile acids might be less toxic if administered via IV infusion, in comparison with oral administration. Then again, they might be more toxic. (Due to rapid excretion or poor absorption via the oral route.) I don't know offhand if one delivery method or the other would be preferred in this regard. But though most bile acids are toxic, not all of them are. TUDCA and UDCA are not only liver-safe, they're first-resort drugs for resolving drug-induced liver damage and promoting liver health. If these "healthy bile acids" can combat MS, that would be a very interesting result. TUDCA and UDCA are very cheap, and their safety profiles are well established.
- coryrc 4y ago
  From other thread: [the tested drug] taurocholic acid is hepatotoxic You: TUDCA and UDCA are not only liver-safe, they're first-resort drugs for resolving drug-induced liver damage Me: I think I have a stupid idea
heavyset_go 4y ago
I have no idea what its metabolic pathways are, but it's possible that by bypassing first pass metabolism might mean that more of the substance reaches the liver versus its metabolites.

citboin 4y ago

tauroursodeoxycholic acid, aka TUDCA. I have M.S. Going to calculate a dose and give it a shot.

heyoni 4y ago
Can you share your result?
nwienert 4y ago
It's been in study for a wide variety of neurodegenerative diseases, with good early results (ALS is one).
ramraj07 4y ago
I sincerely hope you don’t try it without consulting your doctor. EAE mouse models are “like” MS but barely. Something working or not working in EAE models is only a vague suggestion that the same will work or not work on people. This thing can be a supplement but we don’t know how it’ll react with your other medication. The linked article is a fluff piece written by the university PR. According to them every lab in their university is curing cancer and MS and AIDS every day.
- eyelidlessness 4y ago
  I don’t have MS, but I have friends who do and I fully trust them to be appropriately cautious when they react to relevant medical news. They’re among the most medically informed and adept people I know, and not prone to flights of fancy in MS treatment. Maybe some caution is due in lecturing people about how they address dealing with their own illness.
  - jdwithit 4y ago
    That is wonderful for your friends, but I don't know what they have to do with this individual you have never met. My uncle has lived with MS for almost 50 years and is in the final stages of life unfortunately, which I guess gives me the same level of credibility. I would not advise a stranger on the internet to inject themselves with something based on one study done on mice. I'm also not going to tell them what to do with their own body. But "run it by your doctor first" seems like a reasonable thing to suggest, even if they ultimately decide to do it anyway.

deleted 4y ago

[deleted]

FollowingTheDao 4y ago

> taurocholic acid is hepatotoxic. Taurocholic acid is a huma bile acid. I may increase liver enzyme levels with some patients, but to say it is toxic to the liver is fear mongering. https://www.ncbi.nlm.nih.gov/books/NBK548276/ https://www.ncbi.nlm.nih.gov/books/NBK548276/ Not that I think their research is useful in anyway. Anytime you want to treat a disease through a receptor you always end up with changes in receptor density which make the drug useless. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106030/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106030/