4 ms·

I remember from a few few years back that the lipid coating may have caused problems for the liver, when treating people for diseases that needed to target a lo

I remember from a few few years back that the lipid coating may have caused problems for the liver, when treating people for diseases that needed to target a lot of tissue, such as muscle disorders. Is that still the case?

Balgair 1y ago
Unfortunately, I do not know. Sorry here. If anyone else does know, please chime in!
mike_hearn 1y ago
You remember correctly. Moderna had a lot of problems with their drug trials due to the lipid nanoparticles they were using to transport mRNA. They were toxic to the liver upon repeat dosings. Unfortunately, it appears they never found a fix for the problem. Instead they gave up and found a "business solution" by pivoting from drugs to the (at the time) less profitable vaccines, on the grounds that vaccines are something you only need to take once so the toxicity issue could be dodged. Doh. That was in 2017. https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ By the time COVID vaccines came around a few years later there was no evidence they had fixed the problems with lipid nanoparticle delivery. I looked for such evidence extensively at the time, for example, announcements by Moderna of breakthroughs or trials of new drugs. Today the situation seems not much different. Note that Moderna's wikipedia article has a section on "rare disease therapeutics" but it's literally empty: https://en.wikipedia.org/wiki/Moderna#Rare_disease_therapeutics https://en.wikipedia.org/wiki/Moderna#Rare_disease_therapeut... Because of their failure to progress beyond COVID vaccines Moderna's share price got slaughtered, falling from a peak of ~$450 to ~$25 today. I don't know if other companies were able to find breakthroughs here, after COVID I stopped following the topic. Unfortunately, although mRNA tech has great potential, when normal safety standards were reimposed it appears that Moderna went back to being unable to make anything safe enough to launch.
- Jugurtha 1y ago
  What was the success of other means, such as sugars and proteins? Something like glycocalyx or polysaccharide capsules? Or HIV like deployment gp41/gp120?
- Gareth321 1y ago
  > on the grounds that vaccines are something you only need to take once so the toxicity issue could be dodged But we didn't take these vaccines once. We took many of them. Am I to understand a known side effect is liver toxicity for multiple doses?
  - heavyset_go 1y ago
    Toxicity depends on dose. COVID vaccines just need micrograms of material to induce an immune response, I imagine it takes more than that to edit the genes of a large organ.
    - mike_hearn 1y ago
      There have sadly been cases where the vaccines did perform unintended gene editing. It shows up as people whose bodies are still producing spike protein months or years after vaccination.
      - floam 1y ago
        Are you saying that there are cases of longer than expected spike protein presence where these cases are actually because gene editing took place?
        mike_hearn 1y ago
        The Yale LISTEN study found such people for example. Studies on post vaccination heart damage also found free spike protein in the blood of those affected, i.e. the body had turned off the immune response to the spike due to persistent internal production. The most likely way this happened is understood if you dig into it.
        karagenit 1y ago
        Do you have a citation for this? The only relevant study I saw on the LISTEN website was a preprint of a study showing data on self-reported post-vaccine symptoms, but didn’t really talk about causes or gene edits (Krumholz et al. 2023).

Balgair 1y ago

Unfortunately, I do not know. Sorry here. If anyone else does know, please chime in!

mike_hearn 1y ago

You remember correctly. Moderna had a lot of problems with their drug trials due to the lipid nanoparticles they were using to transport mRNA. They were toxic to the liver upon repeat dosings. Unfortunately, it appears they never found a fix for the problem. Instead they gave up and found a "business solution" by pivoting from drugs to the (at the time) less profitable vaccines, on the grounds that vaccines are something you only need to take once so the toxicity issue could be dodged. Doh. That was in 2017. https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ By the time COVID vaccines came around a few years later there was no evidence they had fixed the problems with lipid nanoparticle delivery. I looked for such evidence extensively at the time, for example, announcements by Moderna of breakthroughs or trials of new drugs. Today the situation seems not much different. Note that Moderna's wikipedia article has a section on "rare disease therapeutics" but it's literally empty: https://en.wikipedia.org/wiki/Moderna#Rare_disease_therapeutics https://en.wikipedia.org/wiki/Moderna#Rare_disease_therapeut... Because of their failure to progress beyond COVID vaccines Moderna's share price got slaughtered, falling from a peak of ~$450 to ~$25 today. I don't know if other companies were able to find breakthroughs here, after COVID I stopped following the topic. Unfortunately, although mRNA tech has great potential, when normal safety standards were reimposed it appears that Moderna went back to being unable to make anything safe enough to launch.

Jugurtha 1y ago
What was the success of other means, such as sugars and proteins? Something like glycocalyx or polysaccharide capsules? Or HIV like deployment gp41/gp120?
Gareth321 1y ago
> on the grounds that vaccines are something you only need to take once so the toxicity issue could be dodged But we didn't take these vaccines once. We took many of them. Am I to understand a known side effect is liver toxicity for multiple doses?
- heavyset_go 1y ago
  Toxicity depends on dose. COVID vaccines just need micrograms of material to induce an immune response, I imagine it takes more than that to edit the genes of a large organ.
  - mike_hearn 1y ago
    There have sadly been cases where the vaccines did perform unintended gene editing. It shows up as people whose bodies are still producing spike protein months or years after vaccination.
    - floam 1y ago
      Are you saying that there are cases of longer than expected spike protein presence where these cases are actually because gene editing took place?
      - mike_hearn 1y ago
        The Yale LISTEN study found such people for example. Studies on post vaccination heart damage also found free spike protein in the blood of those affected, i.e. the body had turned off the immune response to the spike due to persistent internal production. The most likely way this happened is understood if you dig into it.
        karagenit 1y ago
        Do you have a citation for this? The only relevant study I saw on the LISTEN website was a preprint of a study showing data on self-reported post-vaccine symptoms, but didn’t really talk about causes or gene edits (Krumholz et al. 2023).