17 ms·

FDA approves a CRISPR-based medicine for treatment of sickle cell disease

535 points by divbzero 3y ago

trident5000 3y ago
Pretty big news. I believe this is the first gene editing therapy approved by the FDA and theres a large backlog thats been in the works for many years. Id like to see the flood gates really open up for gene editing for diseases, preventative treatments, and even cosmetic.
- csdvrx 3y ago
  > Id like to see the flood gates really open up for gene editing for diseases, preventative treatments, and even cosmetic. Me too, because it's fun to consider DNA as some code we can edit to get outcomes we want! However, some people are ethically opposed to that - but piggybacking on the preference people have for having children should be able to move the Overton window!
  - trident5000 3y ago
    It really is inspiring. Yeah I take the opposite side, ethically speaking. I think its cruel to not allow people to fix their bodies in the ways they want and in many cases need. Im in the max body-editing camp. Also this should resolve race issues once and for all which is fun to think about.
    - lotsofpulp 3y ago
      > Also this should resolve race issues once and for all which is fun to think about. I doubt it. One of the root causes of “race” issues is humans using prior probabilities. Unless that changes, then the priors will simply move on from being skin tone based. I would suggest they already have for some portions of the population.
  - JumpCrisscross 3y ago
    > some people are ethically opposed to that Body autonomy may be a fundamental right requiring legal recognition. It curiously cuts across many protracted debates: abortion, vaccine requirements, transgender rights and now gene editing. (I suppose abortion and germ-line edits are a special case.)
elektor 3y ago
Now comes the hard question, how will the US payer system afford it? "An August report from the nonprofit Institute for Clinical and Economic Review found that the treatment and similar gene-editing therapies for sickle cell disease would be cost-effective if priced between $1.35 million and $2.05 million. In the U.S., patients with the condition and their insurers pay on average between $1.6 million and $1.7 million for disease management over the course of a lifetime." Source: https://www.politico.com/news/2023/12/08/fda-gene-editing-therapy-approval-00130814?cid=politico_bsky https://www.politico.com/news/2023/12/08/fda-gene-editing-th...
- codedokode 3y ago
  [flagged]
  - csdvrx 3y ago
    > decided not to have children Most people seem to have a preference for having children. > People must be more responsible. That's another preference, but unfortunately for you it's a minority preference while preferences are averaged (democracry) then encoded (law) at the society level. So what's happening is the opposite: people who prefer not having children will be made to subsidize the costs of these expansive treatments. What's interesting is that there's also a taboo of editing DNA, but this decision shows the societal preference for having children is greater than this taboo. So maybe this taboo is just a preference after all, or a path dependant result due to the precedent of eugenism?
  - iandanforth 3y ago
    You're going to want to avoid using language straight out of GATTACA if you want to have a real conversation on this topic.
    - skullone 3y ago
      We voluntarily did DNA tests on both of us to rule out any parental defects, as well as tests in utero to see if there were issues. Luckily there were none, but we had some discussions on what we might do. It seems reasonable and responsible to perform these tests to be informed on your major life choices.
MiddleEndian 3y ago
Lots of AI content recently (and I am working on AI-adjacent stuff myself lol), but I am most excited for upcoming medical changes. Cure every disease, then let people have designer bodies if they like.
- bigfishrunning 3y ago
  I can't wait to grow all those extra fingers and teeth!
- evrimoztamur 3y ago
  You might enjoy Cronenberg’s Crimes of the Future if that idea is appealing to you. Very curious execution of a disease-free bio-tech (organ-ic-tech?) future.
  - foco_tubi 3y ago
    I just wanna be able to digest plastic
    - numtel 3y ago
      I was wondering about new digestive capabilities recently and wrote this blurb: https://clonk.me/nft/137/0x8abd8d9fab3f711b16d15ce48747db49672eedb2/9 https://clonk.me/nft/137/0x8abd8d9fab3f711b16d15ce48747db496... If we could eat different things, we could give up agriculture and save a bunch of land and energy.
    - MiddleEndian 3y ago
      Speaking of digesting random things, I found myself bored in the shoe section of some store (I wanna say Nordstroms), and I was curious if I could eat the leather shoes. Beef is beef, right? Apparently you cannot digest leather due to the chemicals involved in the curing process.
      - selcuka 3y ago
        > I was curious if I could eat the leather shoes. Beef is beef, right? This was a recurring theme in Lucky Luke [1]. The titular hero cooks and eats his boots when he faces starvation, usually when he gets lost in the desert. [1] https://en.wikipedia.org/wiki/Lucky_Luke https://en.wikipedia.org/wiki/Lucky_Luke
neverrroot 3y ago
Yet another first. Approved, looking forward to more such products, in spite of everything and all the short-term issues, long term is an absolute game changer across the board.
trident5000 3y ago
[flagged]
- hunkins 3y ago
  If you're interested in this, check out Bryan Johnson and Blueprint.
  - Foobar8568 3y ago
    Why anyone would be interested by a charlatan?
    - hunkins 3y ago
      He primarily focuses on sleep, nutrition, and exercise as measurable methods to reduce the speed of aging. Not certain how that makes him a charlatan.
      - lovecg 3y ago
        No, but selling overpriced olive oil with fake health claims does. It’s never “sleep, nutrition, exercise” with those types. It’s “sleep, nutrition, exercise, and this absolutely unique expensive product that you must take everyday that totally works”.
      - ponector 3y ago
        Based on recent history to live up to 100 years you need to become or better to be born a billionaire. Nutrition and exercise could significantly increase quality of life, but not the length.
      - Foobar8568 3y ago
        Yeah, sleep, food and exercise make you healthier, who would have thought. You don't need to create a company claiming to "biohack" and sell products for that, blood transfer ( ! ), or 30 health specialists to monitor how many erection you have over night https://www.insider.com/bryan-johnson-sleeps-with-small-device-on-penis-track-erections-2023-9 https://www.insider.com/bryan-johnson-sleeps-with-small-devi... , I just can't laughing.
KyleSanderson 3y ago
Lyfgenia’s approval came with a black box warning about the possibility that patients who receive the therapy might later develop blood cancer and should be monitored for that risk. Two patients in trials of the drug died of blood cancers, and studies concluded that the cancers were caused by the chemotherapy conditioning regimen for the treatment, not Lyfgenia itself.
- confused_boner 3y ago
  >the cancers were caused by the chemotherapy conditioning regimen for the treatment, not Lyfgenia itself. I am certain some media group is going to conveniently leave this part out of the title of their article, and surely no one is gonna waste time reading the actual article and the rumors will take off.
  - jorlow 3y ago
    The article says "patients must undergo a preparatory treatment with a chemotherapy drug to remove any native stem cells that might remain in their bone marrow." It doesn't make much difference to the patient if it's the Lyfgenia itself or the chemo drug, if the chemo drug is a requirement. Right?
    - confused_boner 3y ago
      I was thinking more that it could poison the reputation of gene therapy by causing folks to falsely associate cancer with gene therapy. And that false stigma could carry on even if one day chemo was no longer needed.
    - eszed 3y ago
      Fair enough, but there remains the possibility of finding an alternate, safer chemotherapy drug. Does anyone know if changing the drug would require a new FDA approval for the entire regimen, or could the protocol be easily changed?
      - firejake308 3y ago
SamBam 3y ago
> Vertex set the price of Casgevy at $2.2 million > Patients must spend weeks, even months, in the hospital before and after the therapy is administered. Yoiks. So how many actual people are going to be able to get this treatment?
- coldpie 3y ago
  Indeed. The good news is, it actually turns out to be about the same or cheaper than ongoing treatment of a untreated sickle cell: """Each treatment is an individualized “one-off” treatment. For this reason, a single treatment for a single patient is expensive. At present it is estimated that in the UK treatment will cost £1 million or more. In the US the estimated cost is $2 million. That may seem prohibitive, but we need to consider the overall cost-effectiveness of the treatment, which means comparing the cost of treatment to the cost of managing each disease without the treatment. Sickle cell patient require frequent hospitalization, which can be very expensive. One analysis found that Casgevy can be cost effective at £1.5 million or $1.9 million. This is in range of the estimated cost. Also, the longer the treatment benefits last, the more cost effective the treatment becomes. A lifetime of transfusions or hospital admissions adds up.""" https://sciencebasedmedicine.org/first-crispr-treatment-approval/ https://sciencebasedmedicine.org/first-crispr-treatment-appr...
  - BurningFrog 3y ago
    Not quite true: Identical twins/triplets/etc, can reuse the same cure.
  - thereisnospork 3y ago
    > it actually turns out to be about the same or cheaper than ongoing treatment of a untreated sickle cell If I were a betting man I'd wager the house that the above is exactly why it costs what it does. 'Pay 2 million now, or pay 2 million over the rest of the patient's life as they suffer' is a pretty inarguable value proposition. Of course once patents expire and processes refine prices will come down. The wheel of progress rolls on (more of less) as intended.
- ericmay 3y ago
mritchie712 3y ago
Ohalo (the company Dave Friedberg is now CEO of) recently got approval for a potato edited by CRISPR: > Ohalo had two RSRs under consideration this year for its potato, one which focuses on higher concentrations of beta carotene – enhancing the overall health and nutrition value of the potato – and another which results in reduced glucose and fructose content in the potato, which, according to Ohalo, will reduce the adverse side effects that lead to significant spoilage during cold storage of potatoes. https://thespoon.tech/gene-edited-food-startup-ohalo-emerges-from-stealth-as-agtech-pioneer-dave-friedberg-takes-the-helm/ https://thespoon.tech/gene-edited-food-startup-ohalo-emerges...
- jabbany 3y ago
  Hmmm. That second one reminds me of the Flavr Savr (https://en.m.wikipedia.org/wiki/Flavr_Savr https://en.m.wikipedia.org/wiki/Flavr_Savr). More shelf life in exchange for likely worse taste...
  - huytersd 3y ago
    Worse taste but probably healthier in this case.
    - SoftTalker 3y ago
      Yeah potatoes will fill your stomach and better than starving but they aren't really healthy food. Eat them in moderation, and prefer sweet potatoes/yams.
      - pastor_bob 3y ago
        >prefer sweet potatoes/yams. Sweet potatoes, as you might expect, have more sugar in them. As do garnet yams. The issue with potatoes isn't really their (low) sugar content.
      - spondylosaurus 3y ago
        On the contrary, potatoes are full of good stuff: https://www.mayoclinichealthsystem.org/hometown-health/speaking-of-health/its-ok-to-say-yes-to-potatoes https://www.mayoclinichealthsystem.org/hometown-health/speak... Just make sure to go easy on the toppings!
downWidOutaFite 3y ago
How do the edited genes replace the body's genes?
- Nasrudith 3y ago
  They technically never do the gene replacement within the body. They take the marrow alter it, grow and produce an external modified new marrow. Chemotherapy wipes out the old bone marrow out and the modified marrow is introduced instead. As breathtakingly advanced and unprecedented as CRISPR treatment is, the execution is still radical and crude by necessity. Not to diminish the accomplishments but to note that we still have a great deal of room to grow. Hopefully knowledge will eventually advance so that less extreme and unpleasant methods will take its place. But that would be a tough nut to crack.
- robwwilliams 3y ago
  No replacement involved. The treatment edits and reactivates the fetal version of HBB gene that is inactivated after birth.
pknerd 3y ago
I wonder whether in the future doctors have a visual designer(WYSIWYG) similar what programmers have in the form of Visual Basic/QT to alter DNA. It'd be pretty interesting if it happens
- huytersd 3y ago
  Also terrifying in a sense. Instead of some wacko shooting up a school, he’s going to make an apocalyptic virus instead.
- quickthrower2 3y ago
  I wonder if they will have a natural language chat interface
w0mbat 3y ago
The gene that causes sickle cell anaemia actually provides partial immunity to malaria, which is why this gene has not been bred out of the population over time.
- lostlogin 3y ago
  > which is why this gene has not been bred out of the population over time. Is that why? Or is it just the people with it aren’t sick enough to die before procreating?
  - freeone3000 3y ago
    In regions where malaria was endemic, this mutation was selected for, as malaria kills children.
  - SoftTalker 3y ago
    Malaria often kills people before they reach the age of being able to procreate.
    - deleted 3y ago
      [deleted]
  - vidarh 3y ago
    Without access to modern hospital treatments it is fairly normal to die very young from sickle cell disease - it causes 100k+ deaths a year. An in-law of an ex has it, and regularly spends days in hospital during crises. Without access to a high quality hospital he'd have been dead a long time ago. The average life expectancy for someone with sickle-cell disease in developed countries is 40-60 years, and serious crises tend to start from childhood. That said, it's recessive, and so it's likely the reverse of what you think: It's not primarily the people with full-blown disease who contributes most to the long term survival of the trait, but that the trait alone confers fairly significant advantage in regions where Malaria is huge killer mostly without causing health problems. So across the combined set of carriers and those with the full disease, the life expectancy in Malaria stricken areas tends to be higher. Pattern of change of the prevalence of the trait correlating with changes in prevalence of Malaria has been observed many places. E.g. the prevalence among US black people is significantly lower and dropping than in the areas their ancestors came from.
joshuamcginnis 3y ago
Here's basically how the process works: * Harvest stem cells from the patient. * Prepare a DNA plasmid with the Cas9 gene, guide RNA for the desired genetic modification, and an antibiotic resistance gene. * Electroporate the plasmid into the harvested stem cells. Grow the electroporated stem cells in antibiotic-containing nutrient media. Only cells with the plasmid (and thus antibiotic resistance) survive. * Expand and freeze the genetically modified cells. * Administer chemotherapy to the patient to eliminate defective bone marrow stem cells. * Inject the modified stem cells back into the patient, where they repopulate the bone marrow with the CRISPR edits, aiming to correct the genetic mutation. This process isn't new but one of the biggest challenges is propagating genetic modifications to all effected cells in the body. This is why it's much easier to GMO an egg / sperm because once the change is made there, it's replicated in every new cell thereafter. Other techniques utilize harmless viruses to transfect genetic modifications to the body, but this has other trade-offs. mRNA vaccines don't propagate to every cell, but the cells which do successfully transcribe the mRNA are able to generate enough of the target protein that the body can recognize it and develop an immunity to it. Eventually, the modified cells will die and no cells will be left to produce the mRNA vaccine protein.
- JumpCrisscross 3y ago
  Do you know why they're having the marrow synthesise fetal hemoglobin versus hemoglobin A(2)? (Is it simply because HbF is one molecule while HbA and HbA2 are two?)
  - joshuamcginnis 3y ago
    Fetal hemoglobin has a lot of biochemical advantages for fighting sickle-cell disease on its own so this is leveraged in the CRISPR solution - e.g. create more of the cells that inhibit the disease in the first place. https://en.wikipedia.org/wiki/Fetal_hemoglobin#Treatment_of_sickle-cell_disease https://en.wikipedia.org/wiki/Fetal_hemoglobin#Treatment_of_...
- sjkoelle 3y ago
  is crispr a big improvement here over AAVs or zinc fingies?
1letterunixname 3y ago
And US patients won't be able to get it because they're going to be overcharged and drowned in debt to the point of bankruptcy.
- marcusverus 3y ago
  Compared to similarly developed countries, Americans are actually in great shape when it comes to debt. See the OECD Data: https://data.oecd.org/hha/household-debt.htm https://data.oecd.org/hha/household-debt.htm
  - matteoraso 3y ago
    Don't be facetious. Parent was obviously referring to medical debt, which most first worlders never have to think about.
    - marcusverus 3y ago
      I wasn’t being facetious, I (wrongly) assumed you could infer the argument: Americans have significantly less debt than Western Europeans. Their average appears to be 50% higher than ours. Including medical debt. The idea, as per GP, that this treatment will inexplicably drive Americans to bankruptcy, is stupid. It’s offensively dumb. It’s the kind of uninformed doomer nonsense that runs rampant online progressive echo chambers, but has no basis in reality. > …which most first worlders never have to think about. Those lucky bastards. With 50% more debt.
- refurb 3y ago
  A very lazy reply. Look at access to the cystic fibrosis therapies ($300,000 per year). The US (including Medicaid) were paying for them from launch in 2012. The UK just came to an agreement for NHS to pay for it in 2020. 8 years later. In Canada, only 5 of the 12 provinces/territories pay for it and only if your a child. Adults don't get it. You actually stand the highest chance of getting it in the US.
dang 3y ago
Recent and related: FDA considers first CRISPR gene editing treatment that may cure sickle cell - https://news.ycombinator.com/item?id=38354939 https://news.ycombinator.com/item?id=38354939 - Nov 2023 (124 comments)
thenerdhead 3y ago
Historic. This opens the door for CRISPR. Very exciting to have followed this in Science/Nature magazine till today.
EvanAnderson 3y ago
The mechanism by which this treatment works is really neat (some notes in [0]). The treatment increases the production of a fetal version of hemoglobin. That fetal hemoglobin is unaffected by the sickle cell mutation. Presumably everybody who is alive (and not a fetus) has a good copy of this fetal hemoglobin gene and it "just" needs re-activated. [0] https://sciencebasedmedicine.org/first-crispr-treatment-approval/ https://sciencebasedmedicine.org/first-crispr-treatment-appr...
user3939382 3y ago
Does anyone who's more familiar with exactly how this works know if this could be applied or potentially applied to thalassemia? From what I understand those are also related to genetically-driven misshapen red blood cells.
- ryankuykendall 3y ago
  CRISPR Therapeutics also has a therapy for Beta Thalassemia in human trials that is up for approval in February 2024. “Editing Humanity” by Kevin Davies covers the history and near future of CRISPR and includes a great chapter on describing both of these therapies.
ezarowny 3y ago
This is such good news! I bet a lot of monogenic disorders are on the table now.
thinkcontext 3y ago
My neighbor has 2 adult children with sickle cell. Its very tough watching what the have to go through. Frequent ambulance visits followed by multiple days in the hospital. Lots of pain in everyday life. The daughter is legally blind from complications. The son tried for a long time to hold a job but couldn't because of how much time he would miss. I hope they are able to get this.
renewiltord 3y ago
Would be interesting if they could do this in embryos.
carabiner 3y ago
Any status updates on the next gen CHEWR?
totorovirus 3y ago
could we have a CRISPR based penis elongation medicine in future? I would like to invest to that startup
- ugh123 3y ago
  Go for curing baldness first
fasteo 3y ago
Every time I read[1] about CRISPR there seem to be concerns about off-target editing, that might cause all kinds of trouble. Is this a solved issue ? Note: I am not a doctor, but I do have a genetic condition that might benefit from CRISPR therapies, hence my interest. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034092/#:~:text=Although%20CRISPR%2FCas%20systems%20exhibit,may%20lead%20to%20adverse%20outcomes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034092/#:~:te....

535 points by divbzero 3y ago

Pretty big news. I believe this is the first gene editing therapy approved by the FDA and theres a large backlog thats been in the works for many years. Id like to see the flood gates really open up for gene editing for diseases, preventative treatments, and even cosmetic.

csdvrx 3y ago
> Id like to see the flood gates really open up for gene editing for diseases, preventative treatments, and even cosmetic. Me too, because it's fun to consider DNA as some code we can edit to get outcomes we want! However, some people are ethically opposed to that - but piggybacking on the preference people have for having children should be able to move the Overton window!
- trident5000 3y ago
  It really is inspiring. Yeah I take the opposite side, ethically speaking. I think its cruel to not allow people to fix their bodies in the ways they want and in many cases need. Im in the max body-editing camp. Also this should resolve race issues once and for all which is fun to think about.
  - lotsofpulp 3y ago
    > Also this should resolve race issues once and for all which is fun to think about. I doubt it. One of the root causes of “race” issues is humans using prior probabilities. Unless that changes, then the priors will simply move on from being skin tone based. I would suggest they already have for some portions of the population.
- JumpCrisscross 3y ago
  > some people are ethically opposed to that Body autonomy may be a fundamental right requiring legal recognition. It curiously cuts across many protracted debates: abortion, vaccine requirements, transgender rights and now gene editing. (I suppose abortion and germ-line edits are a special case.)

elektor 3y ago

Now comes the hard question, how will the US payer system afford it? "An August report from the nonprofit Institute for Clinical and Economic Review found that the treatment and similar gene-editing therapies for sickle cell disease would be cost-effective if priced between $1.35 million and $2.05 million. In the U.S., patients with the condition and their insurers pay on average between $1.6 million and $1.7 million for disease management over the course of a lifetime." Source: https://www.politico.com/news/2023/12/08/fda-gene-editing-therapy-approval-00130814?cid=politico_bsky https://www.politico.com/news/2023/12/08/fda-gene-editing-th...

codedokode 3y ago
[flagged]
- csdvrx 3y ago
  > decided not to have children Most people seem to have a preference for having children. > People must be more responsible. That's another preference, but unfortunately for you it's a minority preference while preferences are averaged (democracry) then encoded (law) at the society level. So what's happening is the opposite: people who prefer not having children will be made to subsidize the costs of these expansive treatments. What's interesting is that there's also a taboo of editing DNA, but this decision shows the societal preference for having children is greater than this taboo. So maybe this taboo is just a preference after all, or a path dependant result due to the precedent of eugenism?
- iandanforth 3y ago
  You're going to want to avoid using language straight out of GATTACA if you want to have a real conversation on this topic.
  - skullone 3y ago
    We voluntarily did DNA tests on both of us to rule out any parental defects, as well as tests in utero to see if there were issues. Luckily there were none, but we had some discussions on what we might do. It seems reasonable and responsible to perform these tests to be informed on your major life choices.

MiddleEndian 3y ago

Lots of AI content recently (and I am working on AI-adjacent stuff myself lol), but I am most excited for upcoming medical changes. Cure every disease, then let people have designer bodies if they like.

bigfishrunning 3y ago
I can't wait to grow all those extra fingers and teeth!
evrimoztamur 3y ago
You might enjoy Cronenberg’s Crimes of the Future if that idea is appealing to you. Very curious execution of a disease-free bio-tech (organ-ic-tech?) future.
- foco_tubi 3y ago
  I just wanna be able to digest plastic
  - numtel 3y ago
    I was wondering about new digestive capabilities recently and wrote this blurb: https://clonk.me/nft/137/0x8abd8d9fab3f711b16d15ce48747db49672eedb2/9 https://clonk.me/nft/137/0x8abd8d9fab3f711b16d15ce48747db496... If we could eat different things, we could give up agriculture and save a bunch of land and energy.
  - MiddleEndian 3y ago
    Speaking of digesting random things, I found myself bored in the shoe section of some store (I wanna say Nordstroms), and I was curious if I could eat the leather shoes. Beef is beef, right? Apparently you cannot digest leather due to the chemicals involved in the curing process.
    - selcuka 3y ago
      > I was curious if I could eat the leather shoes. Beef is beef, right? This was a recurring theme in Lucky Luke [1]. The titular hero cooks and eats his boots when he faces starvation, usually when he gets lost in the desert. [1] https://en.wikipedia.org/wiki/Lucky_Luke https://en.wikipedia.org/wiki/Lucky_Luke

neverrroot 3y ago

Yet another first. Approved, looking forward to more such products, in spite of everything and all the short-term issues, long term is an absolute game changer across the board.

trident5000 3y ago

[flagged]

hunkins 3y ago
If you're interested in this, check out Bryan Johnson and Blueprint.
- Foobar8568 3y ago
  Why anyone would be interested by a charlatan?
  - hunkins 3y ago
    He primarily focuses on sleep, nutrition, and exercise as measurable methods to reduce the speed of aging. Not certain how that makes him a charlatan.
    - lovecg 3y ago
      No, but selling overpriced olive oil with fake health claims does. It’s never “sleep, nutrition, exercise” with those types. It’s “sleep, nutrition, exercise, and this absolutely unique expensive product that you must take everyday that totally works”.
    - ponector 3y ago
      Based on recent history to live up to 100 years you need to become or better to be born a billionaire. Nutrition and exercise could significantly increase quality of life, but not the length.
    - Foobar8568 3y ago
      Yeah, sleep, food and exercise make you healthier, who would have thought. You don't need to create a company claiming to "biohack" and sell products for that, blood transfer ( ! ), or 30 health specialists to monitor how many erection you have over night https://www.insider.com/bryan-johnson-sleeps-with-small-device-on-penis-track-erections-2023-9 https://www.insider.com/bryan-johnson-sleeps-with-small-devi... , I just can't laughing.

KyleSanderson 3y ago

Lyfgenia’s approval came with a black box warning about the possibility that patients who receive the therapy might later develop blood cancer and should be monitored for that risk. Two patients in trials of the drug died of blood cancers, and studies concluded that the cancers were caused by the chemotherapy conditioning regimen for the treatment, not Lyfgenia itself.

confused_boner 3y ago
>the cancers were caused by the chemotherapy conditioning regimen for the treatment, not Lyfgenia itself. I am certain some media group is going to conveniently leave this part out of the title of their article, and surely no one is gonna waste time reading the actual article and the rumors will take off.
- jorlow 3y ago
  The article says "patients must undergo a preparatory treatment with a chemotherapy drug to remove any native stem cells that might remain in their bone marrow." It doesn't make much difference to the patient if it's the Lyfgenia itself or the chemo drug, if the chemo drug is a requirement. Right?
  - confused_boner 3y ago
    I was thinking more that it could poison the reputation of gene therapy by causing folks to falsely associate cancer with gene therapy. And that false stigma could carry on even if one day chemo was no longer needed.
  - eszed 3y ago
    Fair enough, but there remains the possibility of finding an alternate, safer chemotherapy drug. Does anyone know if changing the drug would require a new FDA approval for the entire regimen, or could the protocol be easily changed?
    - firejake308 3y ago

SamBam 3y ago

> Vertex set the price of Casgevy at $2.2 million > Patients must spend weeks, even months, in the hospital before and after the therapy is administered. Yoiks. So how many actual people are going to be able to get this treatment?

coldpie 3y ago
Indeed. The good news is, it actually turns out to be about the same or cheaper than ongoing treatment of a untreated sickle cell: """Each treatment is an individualized “one-off” treatment. For this reason, a single treatment for a single patient is expensive. At present it is estimated that in the UK treatment will cost £1 million or more. In the US the estimated cost is $2 million. That may seem prohibitive, but we need to consider the overall cost-effectiveness of the treatment, which means comparing the cost of treatment to the cost of managing each disease without the treatment. Sickle cell patient require frequent hospitalization, which can be very expensive. One analysis found that Casgevy can be cost effective at £1.5 million or $1.9 million. This is in range of the estimated cost. Also, the longer the treatment benefits last, the more cost effective the treatment becomes. A lifetime of transfusions or hospital admissions adds up.""" https://sciencebasedmedicine.org/first-crispr-treatment-approval/ https://sciencebasedmedicine.org/first-crispr-treatment-appr...
- BurningFrog 3y ago
  Not quite true: Identical twins/triplets/etc, can reuse the same cure.
- thereisnospork 3y ago
  > it actually turns out to be about the same or cheaper than ongoing treatment of a untreated sickle cell If I were a betting man I'd wager the house that the above is exactly why it costs what it does. 'Pay 2 million now, or pay 2 million over the rest of the patient's life as they suffer' is a pretty inarguable value proposition. Of course once patents expire and processes refine prices will come down. The wheel of progress rolls on (more of less) as intended.
ericmay 3y ago

mritchie712 3y ago

Ohalo (the company Dave Friedberg is now CEO of) recently got approval for a potato edited by CRISPR: > Ohalo had two RSRs under consideration this year for its potato, one which focuses on higher concentrations of beta carotene – enhancing the overall health and nutrition value of the potato – and another which results in reduced glucose and fructose content in the potato, which, according to Ohalo, will reduce the adverse side effects that lead to significant spoilage during cold storage of potatoes. https://thespoon.tech/gene-edited-food-startup-ohalo-emerges-from-stealth-as-agtech-pioneer-dave-friedberg-takes-the-helm/ https://thespoon.tech/gene-edited-food-startup-ohalo-emerges...

jabbany 3y ago
Hmmm. That second one reminds me of the Flavr Savr (https://en.m.wikipedia.org/wiki/Flavr_Savr https://en.m.wikipedia.org/wiki/Flavr_Savr). More shelf life in exchange for likely worse taste...
- huytersd 3y ago
  Worse taste but probably healthier in this case.
  - SoftTalker 3y ago
    Yeah potatoes will fill your stomach and better than starving but they aren't really healthy food. Eat them in moderation, and prefer sweet potatoes/yams.
    - pastor_bob 3y ago
      >prefer sweet potatoes/yams. Sweet potatoes, as you might expect, have more sugar in them. As do garnet yams. The issue with potatoes isn't really their (low) sugar content.
    - spondylosaurus 3y ago
      On the contrary, potatoes are full of good stuff: https://www.mayoclinichealthsystem.org/hometown-health/speaking-of-health/its-ok-to-say-yes-to-potatoes https://www.mayoclinichealthsystem.org/hometown-health/speak... Just make sure to go easy on the toppings!

downWidOutaFite 3y ago

How do the edited genes replace the body's genes?

Nasrudith 3y ago
They technically never do the gene replacement within the body. They take the marrow alter it, grow and produce an external modified new marrow. Chemotherapy wipes out the old bone marrow out and the modified marrow is introduced instead. As breathtakingly advanced and unprecedented as CRISPR treatment is, the execution is still radical and crude by necessity. Not to diminish the accomplishments but to note that we still have a great deal of room to grow. Hopefully knowledge will eventually advance so that less extreme and unpleasant methods will take its place. But that would be a tough nut to crack.
robwwilliams 3y ago
No replacement involved. The treatment edits and reactivates the fetal version of HBB gene that is inactivated after birth.

pknerd 3y ago

I wonder whether in the future doctors have a visual designer(WYSIWYG) similar what programmers have in the form of Visual Basic/QT to alter DNA. It'd be pretty interesting if it happens

huytersd 3y ago
Also terrifying in a sense. Instead of some wacko shooting up a school, he’s going to make an apocalyptic virus instead.
quickthrower2 3y ago
I wonder if they will have a natural language chat interface

w0mbat 3y ago

The gene that causes sickle cell anaemia actually provides partial immunity to malaria, which is why this gene has not been bred out of the population over time.

lostlogin 3y ago
> which is why this gene has not been bred out of the population over time. Is that why? Or is it just the people with it aren’t sick enough to die before procreating?
- freeone3000 3y ago
  In regions where malaria was endemic, this mutation was selected for, as malaria kills children.
- SoftTalker 3y ago
  Malaria often kills people before they reach the age of being able to procreate.
  - deleted 3y ago
    [deleted]
- vidarh 3y ago
  Without access to modern hospital treatments it is fairly normal to die very young from sickle cell disease - it causes 100k+ deaths a year. An in-law of an ex has it, and regularly spends days in hospital during crises. Without access to a high quality hospital he'd have been dead a long time ago. The average life expectancy for someone with sickle-cell disease in developed countries is 40-60 years, and serious crises tend to start from childhood. That said, it's recessive, and so it's likely the reverse of what you think: It's not primarily the people with full-blown disease who contributes most to the long term survival of the trait, but that the trait alone confers fairly significant advantage in regions where Malaria is huge killer mostly without causing health problems. So across the combined set of carriers and those with the full disease, the life expectancy in Malaria stricken areas tends to be higher. Pattern of change of the prevalence of the trait correlating with changes in prevalence of Malaria has been observed many places. E.g. the prevalence among US black people is significantly lower and dropping than in the areas their ancestors came from.

joshuamcginnis 3y ago

Here's basically how the process works: * Harvest stem cells from the patient. * Prepare a DNA plasmid with the Cas9 gene, guide RNA for the desired genetic modification, and an antibiotic resistance gene. * Electroporate the plasmid into the harvested stem cells. Grow the electroporated stem cells in antibiotic-containing nutrient media. Only cells with the plasmid (and thus antibiotic resistance) survive. * Expand and freeze the genetically modified cells. * Administer chemotherapy to the patient to eliminate defective bone marrow stem cells. * Inject the modified stem cells back into the patient, where they repopulate the bone marrow with the CRISPR edits, aiming to correct the genetic mutation. This process isn't new but one of the biggest challenges is propagating genetic modifications to all effected cells in the body. This is why it's much easier to GMO an egg / sperm because once the change is made there, it's replicated in every new cell thereafter. Other techniques utilize harmless viruses to transfect genetic modifications to the body, but this has other trade-offs. mRNA vaccines don't propagate to every cell, but the cells which do successfully transcribe the mRNA are able to generate enough of the target protein that the body can recognize it and develop an immunity to it. Eventually, the modified cells will die and no cells will be left to produce the mRNA vaccine protein.

JumpCrisscross 3y ago
Do you know why they're having the marrow synthesise fetal hemoglobin versus hemoglobin A(2)? (Is it simply because HbF is one molecule while HbA and HbA2 are two?)
- joshuamcginnis 3y ago
  Fetal hemoglobin has a lot of biochemical advantages for fighting sickle-cell disease on its own so this is leveraged in the CRISPR solution - e.g. create more of the cells that inhibit the disease in the first place. https://en.wikipedia.org/wiki/Fetal_hemoglobin#Treatment_of_sickle-cell_disease https://en.wikipedia.org/wiki/Fetal_hemoglobin#Treatment_of_...
sjkoelle 3y ago
is crispr a big improvement here over AAVs or zinc fingies?

1letterunixname 3y ago

And US patients won't be able to get it because they're going to be overcharged and drowned in debt to the point of bankruptcy.

marcusverus 3y ago
Compared to similarly developed countries, Americans are actually in great shape when it comes to debt. See the OECD Data: https://data.oecd.org/hha/household-debt.htm https://data.oecd.org/hha/household-debt.htm
- matteoraso 3y ago
  Don't be facetious. Parent was obviously referring to medical debt, which most first worlders never have to think about.
  - marcusverus 3y ago
    I wasn’t being facetious, I (wrongly) assumed you could infer the argument: Americans have significantly less debt than Western Europeans. Their average appears to be 50% higher than ours. Including medical debt. The idea, as per GP, that this treatment will inexplicably drive Americans to bankruptcy, is stupid. It’s offensively dumb. It’s the kind of uninformed doomer nonsense that runs rampant online progressive echo chambers, but has no basis in reality. > …which most first worlders never have to think about. Those lucky bastards. With 50% more debt.
refurb 3y ago
A very lazy reply. Look at access to the cystic fibrosis therapies ($300,000 per year). The US (including Medicaid) were paying for them from launch in 2012. The UK just came to an agreement for NHS to pay for it in 2020. 8 years later. In Canada, only 5 of the 12 provinces/territories pay for it and only if your a child. Adults don't get it. You actually stand the highest chance of getting it in the US.

dang 3y ago

Recent and related: FDA considers first CRISPR gene editing treatment that may cure sickle cell - https://news.ycombinator.com/item?id=38354939 https://news.ycombinator.com/item?id=38354939 - Nov 2023 (124 comments)

thenerdhead 3y ago

Historic. This opens the door for CRISPR. Very exciting to have followed this in Science/Nature magazine till today.

EvanAnderson 3y ago

The mechanism by which this treatment works is really neat (some notes in [0]). The treatment increases the production of a fetal version of hemoglobin. That fetal hemoglobin is unaffected by the sickle cell mutation. Presumably everybody who is alive (and not a fetus) has a good copy of this fetal hemoglobin gene and it "just" needs re-activated. [0] https://sciencebasedmedicine.org/first-crispr-treatment-approval/ https://sciencebasedmedicine.org/first-crispr-treatment-appr...

user3939382 3y ago

Does anyone who's more familiar with exactly how this works know if this could be applied or potentially applied to thalassemia? From what I understand those are also related to genetically-driven misshapen red blood cells.

ryankuykendall 3y ago
CRISPR Therapeutics also has a therapy for Beta Thalassemia in human trials that is up for approval in February 2024. “Editing Humanity” by Kevin Davies covers the history and near future of CRISPR and includes a great chapter on describing both of these therapies.

ezarowny 3y ago

This is such good news! I bet a lot of monogenic disorders are on the table now.

thinkcontext 3y ago

My neighbor has 2 adult children with sickle cell. Its very tough watching what the have to go through. Frequent ambulance visits followed by multiple days in the hospital. Lots of pain in everyday life. The daughter is legally blind from complications. The son tried for a long time to hold a job but couldn't because of how much time he would miss. I hope they are able to get this.

renewiltord 3y ago

Would be interesting if they could do this in embryos.

carabiner 3y ago

Any status updates on the next gen CHEWR?

totorovirus 3y ago

could we have a CRISPR based penis elongation medicine in future? I would like to invest to that startup

ugh123 3y ago
Go for curing baldness first

fasteo 3y ago

Every time I read[1] about CRISPR there seem to be concerns about off-target editing, that might cause all kinds of trouble. Is this a solved issue ? Note: I am not a doctor, but I do have a genetic condition that might benefit from CRISPR therapies, hence my interest. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034092/#:~:text=Although%20CRISPR%2FCas%20systems%20exhibit,may%20lead%20to%20adverse%20outcomes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034092/#:~:te....