What's going on with gene therapies? • Hacker News Board

Re: What's going on with gene therapies?

#21

Post by mandevil » Thu, Jul 17, 2025, 8:08 PM UTC

colechristensen wrote: post #5

JohnMakin wrote: post #2

I have an extremely rare autosomal dominant subtype of a certain genetic disorder that affects maybe less than a few thousand individuals at any one time in the USA. Much common versions of the disorder that affect children have been successfully treated/cured with gene therapy. However gene treatment unlikely to ever reach people like me because so few are affected by it, it's not viable commercially. It's extremely…

One of the sort of strange things about gene therapy is how cheap a custom solution really is. You can arbitrarily genetically modify a plant or bacteria for a few hundred dollars to the level of arbitrarily picking the letters of a gene sequence (or you know, doing some research and doing something real) and getting the gene modifying tools manufactured very very cheaply. If you have a slightly different form of a m…

We are not close to that. Gene therapies are still very much hit or miss in RCT's, if some biohacker offers you something for 5k you are definitely getting scammed.

The first gene therapy approved for in vivo treatment by the FDA, Luxterna, was approved in 2017. It treated RPE65 associated Retinitis Pigmentosa (at an original list price of 425,000/eye). Just a few months ago, J&J's LUMEOS trial revealed that basically the same process but targeting a different gene (RPGR) failed to meet its primary endpoints in the Phase III clinical trial (only 22 of 55 patients treated showed improvement on at least two measures, and there was no statistically significant improvement on the main measure at all). At this point, we can't even reliably take a process that fixed one gene and apply it to another gene to treat the same disease, that's how far away we are from "some dude in a garage." Will we get there? Maybe, but the human body is far more complicated than software, and analogies based on how software work mislead more than they help.

Re: What's going on with gene therapies?

#22

Post by mandevil » Thu, Jul 17, 2025, 8:16 PM UTC

itake wrote: post #14

southernplaces7 wrote: post #10

Earlier quoted context omitted.

My understanding of the comment wasn't that. It was that a solution for his adult version hasn't yet been developed because it's not commercially viable to do so due to its rarity. This of course brings me right back to the points I made in my own comment above. Resources are scarce, and commercial viability, or at least resource viability for all the effort of development, is a factor under any system you choose to…

I think we are saying the same thing. Companies chase high risk high reward over low risk low reward. Presumably, curing a genetic disorder for a very small number of people using existing technology is low risk and low reward. > Why wouldn't it be sold if it were available? Just because something works in a small lab doesn’t mean it’s ready to sell. To launch a product, companies need to do a lot more: testing, cert…

> Presumably, curing a genetic disorder for a very small number of people using existing technology is low risk and low reward.

At the present state of medical understanding, in vivo gene therapy is not low risk, just from a financial perspective, leaving aside the medical risks.

In 2017 the FDA approved Luxterna, the first in vivo gene therapy treatment (it had an original list price of 425,000/eye). It fixed RPE65 associated Retinitis Pigmentosa. This spring J&J announced that their LUMEOS trial had missed its primary endpoint, even though it was basically treating the exact same disease, in the same way, just a different gene (RPGR). But only 22 of the 55 treated patients showed improvements on at least two of their measures, and there was no statistically significant improvement on their primary measure. So this stuff is still very much a financial risk, because we simply don't understand human bodies well enough to predict outcomes in a RCT for gene therapy. And if you have to do a Phase III trial to know whether it works or not, then you are going to be forced to spend a whole lot of money to bring any gene therapy to the market.

Re: What's going on with gene therapies?

#23

Post by JohnMakin » Thu, Jul 17, 2025, 8:24 PM UTC

itake wrote: post #9

southernplaces7 wrote: post #6

Earlier quoted context omitted.

But in all seriousness, who would you direct your anger at in this case? For one thing, being angry in a general sense implies that a fortuitous blend of circumstances is owed to you by the world in a broad sense so that your specific, completely accidental (of nature) misfortune can be remedied. Secondly, many people suffer from much more common conditions that also have no remedy so far (i'm an example of such), an…

I think they are angry because a solution is available but not accessible. People are gatekeeping resources that would enable access to treatment because for big companies, spending $1 to earn $1 isn’t a sustainable business model.

I thought it was pretty clear that's why, but I guess people will read what they will. Not sure why you're being downvoted - it's extremely angering to have a condition that severely limits your quality of life have a cure that society easily has within reach that will likely never become available to you because market forces deemed so. Wouldn't that anger anyone? Like am I supposed to go, "oh gee shucks, that's just the all knowing invisible hand, oh well?"

Weird comment thread. Not bad, just surprises me.

Re: What's going on with gene therapies?

#24

Post by colechristensen » Thu, Jul 17, 2025, 8:34 PM UTC

mandevil wrote: post #21

colechristensen wrote: post #5

Earlier quoted context omitted.

One of the sort of strange things about gene therapy is how cheap a custom solution really is. You can arbitrarily genetically modify a plant or bacteria for a few hundred dollars to the level of arbitrarily picking the letters of a gene sequence (or you know, doing some research and doing something real) and getting the gene modifying tools manufactured very very cheaply. If you have a slightly different form of a m…

We are not close to that. Gene therapies are still very much hit or miss in RCT's, if some biohacker offers you something for 5k you are definitely getting scammed. The first gene therapy approved for in vivo treatment by the FDA, Luxterna, was approved in 2017. It treated RPE65 associated Retinitis Pigmentosa (at an original list price of 425,000/eye). Just a few months ago, J&J's LUMEOS trial revealed that basicall…

If you were a grad student with RP, you could replicate the LUMEOS study drug for $400 + your time for a garage level safety self treatment. I can certainly see someone being willing to take that risk themselves for a 40% chance of improvement to reverse or prevent their own blindness. There are many guardrails for safety which are quite expensive but the actual materials are absolutely not expensive at all.

Re: What's going on with gene therapies?

#25

Post by colechristensen » Thu, Jul 17, 2025, 8:45 PM UTC

rubidium wrote: post #15

colechristensen wrote: post #5

Earlier quoted context omitted.

One of the sort of strange things about gene therapy is how cheap a custom solution really is. You can arbitrarily genetically modify a plant or bacteria for a few hundred dollars to the level of arbitrarily picking the letters of a gene sequence (or you know, doing some research and doing something real) and getting the gene modifying tools manufactured very very cheaply. If you have a slightly different form of a m…

You’ve taken a very small slice of the total workflow to develop cas9 crispr edits. Yes some components are “not crazy expensive”, but that’s not therapeutic production levels. And no sequencing. And no bioinformatics. And then zero tissue targeting/ delivery or safety studies. So $5k is a massive stretch. I do think costs are coming down. But don’t want to oversell current state of “garage hacking” either.

Sequencing all of the interesting parts of the human genome is $300-$400 and a few weeks wait.

The bioinformatics to find a simple mutation and design a crispr fix or one of the other gene therapy methods is about 1 grad student week.

I am talking about garage hacking and there sure are a bunch of risks and chances of ineffective treatments, but researchers used to take a lot more risks and I can see folks with degenerative, terminal, or otherwise very severe conditions being happy to say fuck it let's try something.

And with an appetite for risk and a fuck it attitude, you can try something for less than the cost of a used toyota.

And as mainstream treatments develop, custom gene editing as a fully safe therapy option is going to become common.

Re: What's going on with gene therapies?

#26

Post by mandevil » Thu, Jul 17, 2025, 8:54 PM UTC

colechristensen wrote: post #24

mandevil wrote: post #21

Earlier quoted context omitted.

We are not close to that. Gene therapies are still very much hit or miss in RCT's, if some biohacker offers you something for 5k you are definitely getting scammed. The first gene therapy approved for in vivo treatment by the FDA, Luxterna, was approved in 2017. It treated RPE65 associated Retinitis Pigmentosa (at an original list price of 425,000/eye). Just a few months ago, J&J's LUMEOS trial revealed that basicall…

If you were a grad student with RP, you could replicate the LUMEOS study drug for $400 + your time for a garage level safety self treatment. I can certainly see someone being willing to take that risk themselves for a 40% chance of improvement to reverse or prevent their own blindness. There are many guardrails for safety which are quite expensive but the actual materials are absolutely not expensive at all.

The experience of patients who received Luxterna was that the single most important difference in how large the improvement was and how many complications they had was the quality of the surgeon who delivered the actual therapy. The best surgeons saw much better results and far fewer complications, and these surgeons are way beyond the capability of some grad student in a lab. The best surgeons were way better than other licensed, trained surgeons! That these sorts of non-gene factors dominate the outcomes- and costs- of gene therapy is the point that the original article is making.

The articles example for this is Casgevy, a gene therapy that can mostly cure Sickle Cell. The problem is in order for that gene therapy to work it takes surgeons, full transplant teams, super-chillers, chemotherapy, and full hospitals to deliver it and for the patient to recover in while being carefully monitored. This is what drives the cost, and so it doesn't matter how cheap the actual gene sequencing or editing is, the rest of the costs dominate. This is Amdahl's law, but for costs- the costs are dominated by the non-gene editing part of the process and so that determines the improvement in cost you will see.

Re: What's going on with gene therapies?

#27

Post by l0new0lf-G » Thu, Jul 17, 2025, 8:58 PM UTC

Could it be just that gene therapies should be publicly funded?

Taxpayer money has paid for a substantial percentage of research around the world, and it doesn't seem necessary that we rely on profit-driven private companies for the actual therapies when they could be done at publicly funded hospitals too.

Re: What's going on with gene therapies?

#28

Post by bashmelek » Thu, Jul 17, 2025, 9:01 PM UTC

condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

I have been curious if it would be possible to create a business around pet-genetics as a means to improve the underlying technology without having to be overly concerned about the human factor…granted there will still be ethical restraints of a sort

Re: What's going on with gene therapies?

#29

Post by michaelbrave » Thu, Jul 17, 2025, 9:10 PM UTC

bashmelek wrote: post #28

condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

I have been curious if it would be possible to create a business around pet-genetics as a means to improve the underlying technology without having to be overly concerned about the human factor…granted there will still be ethical restraints of a sort

More likely the profit would then be in dealing with animal husbandry types of modifications instead. Cows/chickens that don't get sick, that kind of thing.

Re: What's going on with gene therapies?

#30

Post by michaelbrave » Thu, Jul 17, 2025, 9:13 PM UTC

mandevil wrote: post #19

condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

This is actually a lot harder than you think because we still don't understand gene therapy well enough to be able to be sure that any given treatment works without the really expensive part, the Randomized Control Trial. In 2017 a gene therapy was approved in the US for RPE65-associated Retinitis Pigmentosa, Luxterna, the first in-vivo gene therapy approved by the FDA (yay! List price was a mere 425,000/eye). Just a…

I think a lot of our diseases if looked at genetically instead of symptoms-wise that we will probably find out that it's actually multiple conditions that we just group together for manifesting in similar ways. I've felt this in my own life with ADHD things where it seems to me that there are at least 3-4 different types of ADHD and that they respond to treatments/medications differently, and this makes me think that many other conditions might be similar, especially if we start looking at them genetically.