Third patient dies from acute liver failure caused by a Sarepta gene therapy
27 comments
·July 18, 2025snitty
mattigames
If the institutions of science and technology lasted thousands of years evolution would prefer people with the less hardened firmware, as in, the ones to survive and pass their genes would be the ones with the most "hackable" genes.
DangerousPie
https://www.science.org/content/blog-post/sarepta-sarepta
Thoughts from Derek Lowe (In The Pipeline).
perihelions
Also Derek Lowe's previous ones as context (subset I could quickly find),
https://www.science.org/content/blog-post/sarepta-s-approval... ("Sarepta's Approval Woes" (2013))
https://www.science.org/content/blog-post/sarepta-s-duchenne... ("Sarepta's Duchenne Therapy Is A Lot Further Away" (2014))
https://www.science.org/content/blog-post/sarepta-s-day-fda ("Sarepta's Day at the FDA " (2016))
https://www.science.org/content/blog-post/sarepta-gets-appro... ("Sarepta Gets An Approval - Unfortunately" (2016))
https://www.science.org/content/blog-post/gene-therapy-duche... ("Gene Therapy for Duchenne" (2018))
https://www.science.org/content/blog-post/opening-lid-sarept... ("Opening the Lid on Sarepta's Drug Approvals" (2020))
https://www.science.org/content/blog-post/sarepta-tries-agai... ("Sarepta Tries Again" (2023))
https://www.science.org/content/blog-post/sarepta-why ("Sarepta. Why?" (2024))
forgotpwagain
A thread from yesterday about why gene therapy hasn't reached its potential: https://news.ycombinator.com/item?id=44573193
Flux159
A bloomberg archive.ph article about the same topic - https://archive.ph/9qB0t
simmerup
Damn, gene therapy is so promising too
barbarr
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.
amelius
Could hemodialysis prevent this?
EA-3167
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.
wiz21c
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")
cyberax
Lipid nanoparticles have exactly the same problem. They mostly concentrate in the liver.
sampl3username
Sarepta's drug uses AAV to deliver the payload. I wonder why they chose AAV instead of lipid nanoparticles.
https://medcitynews.com/2025/07/sarepta-gene-therapy-fatalit...
barbarr
I'm guessing they were looking for preferential delivery to certain cell types, and AAVs just happened to have best profile for those. If anything, LNPs might aggregate in the liver even more than AAVs, which can lead to even worse hepatotoxicity if an immune response happens.
sampl3username
I thought lipid nanoparticles were less prone to generate a immune reaction.
snitty
This gene therapy involves a gene called dystrophin, which is one of if not the largest gene in the human genome. Sarepta is actually using a version called microdystrophin, which is a truncated version. It still barely fits into AAV.
Reasons to use AAV: they're going for sustained production of the therapeutic gene, and AAVs are better at doing that than LNPs. LNPs were used in the mRNA COVID vaccine, because they're great at transient production.
To get stable production from an LNP you'd likely have to integrate into the genome, which risks cancer from disrupting oncogenes. You'd also need to package the therapeutic gene with a mechanism of integrating into the genome, like recombinase.
ceejayoz
Probably because the HHS secretary is vehemently opposed to lipid nanoparticles.
https://www.axios.com/2025/04/18/rfk-jrs-potential-future-ta...
https://kffhealthnews.org/news/article/nih-grants-mrna-vacci...
> National Institutes of Health officials have urged scientists to remove all references to mRNA vaccine technology from their grant applications, two researchers said, in a move that signaled the agency might abandon a promising field of medical research.
SoftTalker
They've been working on this for years. It's not anything to do with the current administration.
downrightmike
Yeah, if not for Germany, the covid vax wouldn't have been unreachable.
fsckboy
the paywall really cuts down on the readability of this story. a quick google showed plenty of news stories though, their shareprice dropped 40% on the market today.
I'd be curious what the numbers are for the "good" that this therapy does; is there any way that this therapy is still "worth it" at any scale? but I know little about this area so that's a fairly naive question.
OsrsNeedsf2P
Their stock is down 90% over the last 6 months, 37% today. That's not good.
NooneAtAll3
stock price barely mean anything in recent years
financetechbro
Not for biotech. The stocks in this segment are very sensitive to trial outcomes and drug efficacy
bboygravity
Stocks in biotech also very sensitive to coordinated naked shorting and cellar boxing by hedge funds.
null
I've been working on a piece about how humans effectively have hardened firmware, and gene therapies need to do A LOT to try to get around the various defenses our bodies evolved. I should probably finish that article...