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Comment by barbarr | Hacker News Reader

The issue was not the gene therapy itself, but the delivery mechanism. They used a virus to administer the gene therapy, and this virus (like most bloodstream impurities) aggregates in the liver. At low doses this is fine, but at high doses, your body's immune response will be laser-focused on the liver, and you die from the side effects of this response.

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Lipid nanoparticles have exactly the same problem. They mostly concentrate in the liver.

Wouldn't anything concentrate in the liver?

if it's so obvious that this is going to produce these side effects, then why on earth did they gamble ?

(because, it definitely look like gambling, like "investors are behind us right now, so we have the money to do it, so let's do it before money runs out")

My brother in commenting they are doing trials. Trials are by nature bets. That’s how we move science forward.

They’re not trying to kill people. There is a hell of a lot more money in _not_ killing people.

Could hemodialysis prevent this?

Yes, dialysis is surprisingly good at filtering out viral particles, but... that's not desirable in this case. After all these viruses are carrying the therapeutic payload, if you filter them out then you might as well not introduce them in the first place.

But maybe as treatment if liver problems are detected?

I suppose it's possible at that point, possibly to try and stem the process. The question is just how rapidly this condition emerges, and I suspect (although this is just a suspicion) that the time between onset and a severe reaction is fairly brief. Mostly though the problem is that this is a really complex, whole immune system reaction that's triggered by the AAV in the liver, but simply removing the intial cause probably wouldn't stop the cascade.

I took a look at some of the aftermath reports (i.e. https://pmc.ncbi.nlm.nih.gov/articles/PMC10638066/ and some others) which get into specific details about the course of treatment in several patients who died from this complication. The through-line is an aggressive use of several immune suppressing and modulating therapies to calm the cascade.

I have to admit I can't find any specific discussion about dialysis in that context, so I can only assume that removal of the viral particles would be a case of closing the barn door after the horse escaped.

Yeah I was suspecting they would do the treatment with immunosuppressants. Immune response is an unpredictable killer.

Ok, I was thinking more of injecting viruses upstream, and filtering them out downstream (preventing them from entering the liver in the first place). Maybe you could even recycle them.

I imagine if these deaths could have been prevented by this one-line HN comment, they would have thought of it.

Maybe a better phrasing of your question would be:

> Why is hemodialysis ineffective for this?

The main reason for my question was this:

https://news.ycombinator.com/item?id=44609583

Hacker News Guidelines > "Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes."

My bad, snark wasn't my intent. I meant it literally. There was an accumulation of toxins, and it seems (to me at least) extremely unlikely that the researchers were not aware of dialysis as a way to remove toxins. So then let's jump to the next level of question.

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