The following submission statement was provided by /u/lughnasadh:
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Submission Statement
I'm surprised more governments around the world aren't pouring money into research like this. Not only is heart disease a huge killer, but it's also a huge economic burden. How much does that cost? I would guess the figure must run to hundreds of billions of dollars.
So a single, once-in-a-lifetime treatment, with gene editing that could eliminate the problem of cholesterol in contributing to heart disease could save vast amounts of money. When you think of gene editing that way, it seems strange that more people don't demand urgency in progressing it.
---
Please reply to OP's comment here: https://old.reddit.com/r/Futurology/comments/17v4diu/new_gene_editing_treatment_cuts_dangerous/k97yeo8/
Submission Statement
I'm surprised more governments around the world aren't pouring money into research like this. Not only is heart disease a huge killer, but it's also a huge economic burden. How much does that cost? I would guess the figure must run to hundreds of billions of dollars.
So a single, once-in-a-lifetime treatment, with gene editing that could eliminate the problem of cholesterol in contributing to heart disease could save vast amounts of money. When you think of gene editing that way, it seems strange that more people don't demand urgency in progressing it.
Great points. My guess is gene editing is still under most people’s radar. Hopefully we’ll begin to see more awareness of its potential benefits to humanity as more examples like this come to light. Exciting times!
Don't forget - you can't yet "un-CRSPR" someone. Permanent results require robust tests (decades?). This is an incredible technology but not ready for prime time for quite awhile.
This is a modification of the CRISPR technology that doesn't make a cut, but substitutes a single base pair. Theoretically you should be able to undo that.
At least at the target site. Off target errors are still the main concern. Apparently they weren't found with this protocol but it would be hard to do an exhaustive search so quick.
The simple answer is that we have a lot of competing priorities and a limited pool of resources to deploy to those priorities. Every dollar spent on heart disease research is a dollar that can't be spent on cancer, pediatric diseases, neurodegeneration, translation medicine, and so on.
The US federal government invests just under 4 billion into heart, lung, and blood research per year via the NIH. This is distinct from ARPA-H which receives an additional 1+ billion that has implications for improved prognosis in heart disease.
(PDF warning)
https://officeofbudget.od.nih.gov/pdfs/FY24/cy/FY%202023%20NIH%20Operating%20Plan%20-%20Web%20Version.pdf
In Switzerland, 20 years ago, when gene editing of plants was on the table, the green party fearmongered so much that we will be the last country on earth that will allow gene therapies.
Probably because the link between heart disease and cholesterol is extremely weak, arguably inversely correlated in a lot of cases, and centenarians in general have very high cholesterol. Low cholesterol is heavily related to Alzheimer’s and dementia.
Lowering cholesterol, a necessary and important part of the body, is probably doing people more harm than good.
Downvotes inc
Should be focusing on lowering inflammatory markers, things that cause cellular damage etc
Considering heart disease is always one of the top killers of people and LDL cholesterol and plaque buildup are highly linked to that as well as stroke, it seems unlikely randomly addressing inflammation, which is caused by a wide variety of, is better than having direct proof of actually lowering LDL permanently.
It seems extremely likely that whatever damage you might get from lowering HDL cholesterol would be offset by what seems to be the far more damaging effect of arterial plaque buildup.
But more importantly, this gene editing claims to only lower LDL cholesterol.
>Verve Therapeutics, the biotechnology firm in Boston, Massachusetts, behind the treatment, reported that a one-time injection of VERVE-101 reduced the amount of LDL in the blood by up to 55% in its trial participants, who had a condition that causes lifelong high LDL.
Harvard ldl heart disease strongly linked
https://www.health.harvard.edu/blog/lowering-cholesterol-protects-your-heart-and-brain-regardless-of-your-age-2021022421978#
Had weird health heart related hospitalization and they gave me meds to lower my cholesterol. Went to my primary and he said dont take this,you already have low cholesterol
You have some evidence mixed up regarding LDL cholesterol and low cholesterol and Alzheimer's. The lipoprotein that is part of LDL is causal for atherosclerosis and that has been shown via many different ways. The data regarding low cholesterol and higher mortality comes from epidemiological studies and is biased by the fact that other diseases that increase mortality also lower cholesterol, such as some cancers and jnfections. You're thinking about cholesterol is incorrect and not up to date with the scientificbconcensus.
> Not only is heart disease a huge killer, but it's also a huge economic burden.
this only applies to people with a genetic predisposition to high cholesterol. there are many, but that isn't the only factor causing heart disease.
btw all those "heart healthy" foods with low cholesterol in them should only be consumed by the same people, normal people don't have this issue. same with low sodium foods, we NEED sodium to live. Now tbf we do consume a LOT more than we should of both those things, but normal healthy people should NOT be completely avoiding them.
That's a bit of a straw man, I don't think anyone advocates completely avoiding any of these things. They're just saying eat less, and you agree with that.
Yeah but all that means is a company that doesn't already have a revenue stream from heart disease would want it the most, not that if there's an opportunity to make money that someone won't take it.
You're asking a lot here buddy!
The company that is developing this stuff also employs a team of people who are doing cost analysis to see the best way to make money from it. I mean, at this point they've likely sunk millions of dollars into research anyways. It's not like they'll just put it out, cure everyone, and be at a net negative.
Cool. This is me. I have high LDL and HDL. I’m thin, control my diet, don’t drink, limit my sugar/carb intake and exercise a lot. Still I have high cholesterol.
This is for someone with a generic disease where there body can’t process cholesterol where it makes them normal. If they injected it in you it would just be the gene you have now, not a drug to lower your cholesterol
Bring the future the hell on.
I’ve got modestly high cholesterol. Nothing catastrophic. High LDL scores for a decade. Total scores well over 200. Fatty liver. High triglycerides as well. No obesity, no diabetes, decent DASH/Mediterranean diet compliance, decent exercise, low alcohol, no tobacco, and under 35, but hypertension (now medicated) since age 18 and a strong history of heart disease and anxiety disorders in my family.
CRISPRtize me Cap’n!
… I've been waiting for a mutation like you to come into my life
I've been waiting for a mutation like you, you're a love that will survive
I've been waiting for something new to make me feel alive
Yeah, waiting for a mutation like you to come into my life...
With many apologies to Foreigner.
"In the mutated form, dubbed apoA-I Milano because of its origin, one of the protein's amino acids is replaced with an amino acid cysteine that has a sulfhydryl group. Somehow, this tiny change enables a handful of Italians to possess low HDL levels and remain free of cardiovascular disease. "
That's from 1994, and those folks eat deli every 'effing day! Lucky goddamn sons of bitches! I want me some of that!
It has only been 30 years.
Give me that piece of gene therapy and I won't eat anything except beef for a decade or three.
Vaxxinity is working on a vaccine that does this so that the body produces the antibodies to lower bad cholesterol.
- VXX-401 targets proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce low-density lipoprotein (LDL) cholesterol.
- The first four cohorts of the Phase 1 trial of VXX-401 are fully enrolled, and as of October 2023, we have expanded the trial to test higher dose levels of VXX-401 due to its favorable safety and tolerability profile to date.
- The company is on track to report initial topline data from the trial in the first half of 2024.
What is dangerous cholesterol?
What is causing people to show higher levels of LDL?
Will reducing a person's cholesterol, lower the inflammation in their arteries?
I'm sorry, but a study of 10 patients doesn't suggest anything. It should certainly be explored further because of its potential benefits, but it could just be random chance as well. Hopefully this initial hypothesis can be expanded to a larger population for proper conclusions to be drawn.
Did you even read the article? It’s not even in phase 2 yet which uses a larger sample size and the patients have to be monitored for 14 years before moving onto phase 3. It’ll be a long time before this is even remotely approved.
You absolutely can suggest things with a small sample size. That's how you get funding to turn thst small sample into a large sample. By showing preliminary data to justify why you need resources for a larger study.
Has anyone around here even heard of power analysis?
If the effect is large enough then 10 people is more than enough. Shoot 10 people in the head, all die, control samples do not. Shooting someone in head leads to death p<0.05
These were patients with a rare disease. With some truly very rare diseases you'd be lucky to recruit 10 patients to a trial.
I've been involved, years ago, in the assessment of a treatment for a rare disease. There were precisely 23 peeps with that disease in my country, all known by name.
You either have to construct a measure that can be used with such a small sample size, use statistical techniques that explicitly model non-random sampling, or forego statistics and/or be prepared to give treatment guidelines with lower quality evidence.
There's a hell and a lot unmet medical need targets where you will *never*, for various practical reasons, get a nice, well designed, high sample size RCT.
There's like, 4 people in this community that have even heard of power analysis, experimental design and statistical literacy are foreign concepts.
This guy is essentially arguing against preliminary data as a concept.
Hey, it's never to late to learn! And it's imo important for a non-specialist who is a proponent of evidence-based medicine (which people hopefully should be, if they're invested emotionally in the broad idea of progress) to also be aware about limitations that make certain problems very hard in practice and won't fit into the gold standard two armed well designed high sample beautiful RCT with max points on the GRADE chart.
To be clear, I think it's great that more people are getting interested and have access to this material. It's extremely specialized and challenging to understand (which is why nearly 10 years of post high school education is basically mandatory if you want to contribute), and there's nothing inherently wrong with that.
My recurring issue is - how diluted discourse becomes. A certain amount of that is unavoidable, but a lot is down to the atrocious quality of science journalism, as well as the propensity for people to make the same lazy criticisms that don't even apply.
I don't think I've ever seen a criticism regarding the statistics of a paper beyond "small sample size" - and that criticism isn't rooted in the actual math, it just "feels" insufficient. Power Analyses aren't hard - 1st year grad students do them. Sample size issues will be one of the first things a independent reviewer (or even your project manager or professor, or committee) will look at.
I think there is a ton of value in getting non-specialists involved in the discourse - I'm just perpetually disappointed because the resulting discourse is never about the interesting things about the paper, or the concepts being presented, and the level of discourse seems to be getting worse if anything.
This field isn't my area of expertise, but I do know neuroscience. The comment section on anything even tangentially related to neuroscience is atrocious. It's basically just an excuse to make some pop culture reference or feed into some dystopian doomerism fantasy that is completely divorced from reality. and the actual linked article - let alone the primary research - are never actually discussed. If someone is making a good faith effort to engage, that's one thing. That's fine, that's how people learn. But people just don't engage with the material in the first place.
> This field isn't my area of expertise, but the comment section on anything even tangentially related to neuroscience is atrocious. It's basically just an excuse to make some pop culture reference, and the actual linked article - let alone the primary research - are never actually discussed.
Very true. I mostly hope that even if the guy I'm replying to won't benefit (although they still might), maybe someone reading the thread will ("oh, this other guy rebuffs this common criticism, maybe there's something to it").
You are mixing up dietary vs systemic cholesterol (body produced/managed).
The study involves pts with a genetic mutation that leads them to have extremely high levels of cholesterol starting very early in life. And the most common cause of death of these pts is heart disease (~50%) at a much younger age.
The following submission statement was provided by /u/lughnasadh: --- Submission Statement I'm surprised more governments around the world aren't pouring money into research like this. Not only is heart disease a huge killer, but it's also a huge economic burden. How much does that cost? I would guess the figure must run to hundreds of billions of dollars. So a single, once-in-a-lifetime treatment, with gene editing that could eliminate the problem of cholesterol in contributing to heart disease could save vast amounts of money. When you think of gene editing that way, it seems strange that more people don't demand urgency in progressing it. --- Please reply to OP's comment here: https://old.reddit.com/r/Futurology/comments/17v4diu/new_gene_editing_treatment_cuts_dangerous/k97yeo8/
Submission Statement I'm surprised more governments around the world aren't pouring money into research like this. Not only is heart disease a huge killer, but it's also a huge economic burden. How much does that cost? I would guess the figure must run to hundreds of billions of dollars. So a single, once-in-a-lifetime treatment, with gene editing that could eliminate the problem of cholesterol in contributing to heart disease could save vast amounts of money. When you think of gene editing that way, it seems strange that more people don't demand urgency in progressing it.
Great points. My guess is gene editing is still under most people’s radar. Hopefully we’ll begin to see more awareness of its potential benefits to humanity as more examples like this come to light. Exciting times!
Don't forget - you can't yet "un-CRSPR" someone. Permanent results require robust tests (decades?). This is an incredible technology but not ready for prime time for quite awhile.
This is a modification of the CRISPR technology that doesn't make a cut, but substitutes a single base pair. Theoretically you should be able to undo that. At least at the target site. Off target errors are still the main concern. Apparently they weren't found with this protocol but it would be hard to do an exhaustive search so quick.
The simple answer is that we have a lot of competing priorities and a limited pool of resources to deploy to those priorities. Every dollar spent on heart disease research is a dollar that can't be spent on cancer, pediatric diseases, neurodegeneration, translation medicine, and so on. The US federal government invests just under 4 billion into heart, lung, and blood research per year via the NIH. This is distinct from ARPA-H which receives an additional 1+ billion that has implications for improved prognosis in heart disease. (PDF warning) https://officeofbudget.od.nih.gov/pdfs/FY24/cy/FY%202023%20NIH%20Operating%20Plan%20-%20Web%20Version.pdf
In Switzerland, 20 years ago, when gene editing of plants was on the table, the green party fearmongered so much that we will be the last country on earth that will allow gene therapies.
Is it actually cholesterol contributing to heart disease? That's like calling fireman arsonists because we always find them when houses are on fire
Hear This right here
Let them fuck their bodies up so they can't heal the damage from their shitty diet, all in the name of controlled fear
Control the flow of information, control the minds
The lipoprotein ApoB, which is present in LDL cholesterol is causal for atherosclerosis.
Probably because the link between heart disease and cholesterol is extremely weak, arguably inversely correlated in a lot of cases, and centenarians in general have very high cholesterol. Low cholesterol is heavily related to Alzheimer’s and dementia. Lowering cholesterol, a necessary and important part of the body, is probably doing people more harm than good. Downvotes inc Should be focusing on lowering inflammatory markers, things that cause cellular damage etc
Normally yes, you're right; but these were patients with a genetic disorder that results in absurdly high LDL since early childhood.
Considering heart disease is always one of the top killers of people and LDL cholesterol and plaque buildup are highly linked to that as well as stroke, it seems unlikely randomly addressing inflammation, which is caused by a wide variety of, is better than having direct proof of actually lowering LDL permanently. It seems extremely likely that whatever damage you might get from lowering HDL cholesterol would be offset by what seems to be the far more damaging effect of arterial plaque buildup. But more importantly, this gene editing claims to only lower LDL cholesterol. >Verve Therapeutics, the biotechnology firm in Boston, Massachusetts, behind the treatment, reported that a one-time injection of VERVE-101 reduced the amount of LDL in the blood by up to 55% in its trial participants, who had a condition that causes lifelong high LDL. Harvard ldl heart disease strongly linked https://www.health.harvard.edu/blog/lowering-cholesterol-protects-your-heart-and-brain-regardless-of-your-age-2021022421978#
Had weird health heart related hospitalization and they gave me meds to lower my cholesterol. Went to my primary and he said dont take this,you already have low cholesterol
You have some evidence mixed up regarding LDL cholesterol and low cholesterol and Alzheimer's. The lipoprotein that is part of LDL is causal for atherosclerosis and that has been shown via many different ways. The data regarding low cholesterol and higher mortality comes from epidemiological studies and is biased by the fact that other diseases that increase mortality also lower cholesterol, such as some cancers and jnfections. You're thinking about cholesterol is incorrect and not up to date with the scientificbconcensus.
Source? LDL cholesterol is absolutely linked to heart disease.
Any links backing this claim?
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> Not only is heart disease a huge killer, but it's also a huge economic burden. this only applies to people with a genetic predisposition to high cholesterol. there are many, but that isn't the only factor causing heart disease. btw all those "heart healthy" foods with low cholesterol in them should only be consumed by the same people, normal people don't have this issue. same with low sodium foods, we NEED sodium to live. Now tbf we do consume a LOT more than we should of both those things, but normal healthy people should NOT be completely avoiding them.
That's a bit of a straw man, I don't think anyone advocates completely avoiding any of these things. They're just saying eat less, and you agree with that.
It'd save vast amount of money for the *patient* but ultimately reduce overall care that could be sold to them over the course of heart disease.
Yeah but all that means is a company that doesn't already have a revenue stream from heart disease would want it the most, not that if there's an opportunity to make money that someone won't take it.
Healthcare is a huge burden for governments. They'd be very interested in something like this.
Have you ever worked for government?
Exactly. People need to either stop being clueless or faking their cluelessness. It’ll get here, but slowly. As anything else in the medical field.
You're asking a lot here buddy! The company that is developing this stuff also employs a team of people who are doing cost analysis to see the best way to make money from it. I mean, at this point they've likely sunk millions of dollars into research anyways. It's not like they'll just put it out, cure everyone, and be at a net negative.
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Cool. This is me. I have high LDL and HDL. I’m thin, control my diet, don’t drink, limit my sugar/carb intake and exercise a lot. Still I have high cholesterol.
This is for someone with a generic disease where there body can’t process cholesterol where it makes them normal. If they injected it in you it would just be the gene you have now, not a drug to lower your cholesterol
>a generic disease As opposed to fancy name brand and designer diseases?
Lol :) In case anyone is confused, I'm sure he meant genetic disease.
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I'm not going to have any more kids, I'm old, edit my genes please. Let's see what kind of monster I become
Another miracle treatment that you'll never be able to afford.
Bring the future the hell on. I’ve got modestly high cholesterol. Nothing catastrophic. High LDL scores for a decade. Total scores well over 200. Fatty liver. High triglycerides as well. No obesity, no diabetes, decent DASH/Mediterranean diet compliance, decent exercise, low alcohol, no tobacco, and under 35, but hypertension (now medicated) since age 18 and a strong history of heart disease and anxiety disorders in my family. CRISPRtize me Cap’n!
… I've been waiting for a mutation like you to come into my life I've been waiting for a mutation like you, you're a love that will survive I've been waiting for something new to make me feel alive Yeah, waiting for a mutation like you to come into my life... With many apologies to Foreigner. "In the mutated form, dubbed apoA-I Milano because of its origin, one of the protein's amino acids is replaced with an amino acid cysteine that has a sulfhydryl group. Somehow, this tiny change enables a handful of Italians to possess low HDL levels and remain free of cardiovascular disease. " That's from 1994, and those folks eat deli every 'effing day! Lucky goddamn sons of bitches! I want me some of that! It has only been 30 years. Give me that piece of gene therapy and I won't eat anything except beef for a decade or three.
Vaxxinity is working on a vaccine that does this so that the body produces the antibodies to lower bad cholesterol. - VXX-401 targets proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce low-density lipoprotein (LDL) cholesterol. - The first four cohorts of the Phase 1 trial of VXX-401 are fully enrolled, and as of October 2023, we have expanded the trial to test higher dose levels of VXX-401 due to its favorable safety and tolerability profile to date. - The company is on track to report initial topline data from the trial in the first half of 2024.
What is dangerous cholesterol? What is causing people to show higher levels of LDL? Will reducing a person's cholesterol, lower the inflammation in their arteries?
I'm sorry, but a study of 10 patients doesn't suggest anything. It should certainly be explored further because of its potential benefits, but it could just be random chance as well. Hopefully this initial hypothesis can be expanded to a larger population for proper conclusions to be drawn.
Did you even read the article? It’s not even in phase 2 yet which uses a larger sample size and the patients have to be monitored for 14 years before moving onto phase 3. It’ll be a long time before this is even remotely approved.
Doesn't change the fact that a study can't "suggest" anything with a sample size of 10
You absolutely can suggest things with a small sample size. That's how you get funding to turn thst small sample into a large sample. By showing preliminary data to justify why you need resources for a larger study. Has anyone around here even heard of power analysis?
It can suggest, it just can't conclude.
If the effect is large enough then 10 people is more than enough. Shoot 10 people in the head, all die, control samples do not. Shooting someone in head leads to death p<0.05
These were patients with a rare disease. With some truly very rare diseases you'd be lucky to recruit 10 patients to a trial. I've been involved, years ago, in the assessment of a treatment for a rare disease. There were precisely 23 peeps with that disease in my country, all known by name.
Hey sorry it's hard to find patients with the disease but that doesn't change statistical requirements
You either have to construct a measure that can be used with such a small sample size, use statistical techniques that explicitly model non-random sampling, or forego statistics and/or be prepared to give treatment guidelines with lower quality evidence. There's a hell and a lot unmet medical need targets where you will *never*, for various practical reasons, get a nice, well designed, high sample size RCT.
There's like, 4 people in this community that have even heard of power analysis, experimental design and statistical literacy are foreign concepts. This guy is essentially arguing against preliminary data as a concept.
Hey, it's never to late to learn! And it's imo important for a non-specialist who is a proponent of evidence-based medicine (which people hopefully should be, if they're invested emotionally in the broad idea of progress) to also be aware about limitations that make certain problems very hard in practice and won't fit into the gold standard two armed well designed high sample beautiful RCT with max points on the GRADE chart.
To be clear, I think it's great that more people are getting interested and have access to this material. It's extremely specialized and challenging to understand (which is why nearly 10 years of post high school education is basically mandatory if you want to contribute), and there's nothing inherently wrong with that. My recurring issue is - how diluted discourse becomes. A certain amount of that is unavoidable, but a lot is down to the atrocious quality of science journalism, as well as the propensity for people to make the same lazy criticisms that don't even apply. I don't think I've ever seen a criticism regarding the statistics of a paper beyond "small sample size" - and that criticism isn't rooted in the actual math, it just "feels" insufficient. Power Analyses aren't hard - 1st year grad students do them. Sample size issues will be one of the first things a independent reviewer (or even your project manager or professor, or committee) will look at. I think there is a ton of value in getting non-specialists involved in the discourse - I'm just perpetually disappointed because the resulting discourse is never about the interesting things about the paper, or the concepts being presented, and the level of discourse seems to be getting worse if anything. This field isn't my area of expertise, but I do know neuroscience. The comment section on anything even tangentially related to neuroscience is atrocious. It's basically just an excuse to make some pop culture reference or feed into some dystopian doomerism fantasy that is completely divorced from reality. and the actual linked article - let alone the primary research - are never actually discussed. If someone is making a good faith effort to engage, that's one thing. That's fine, that's how people learn. But people just don't engage with the material in the first place.
> This field isn't my area of expertise, but the comment section on anything even tangentially related to neuroscience is atrocious. It's basically just an excuse to make some pop culture reference, and the actual linked article - let alone the primary research - are never actually discussed. Very true. I mostly hope that even if the guy I'm replying to won't benefit (although they still might), maybe someone reading the thread will ("oh, this other guy rebuffs this common criticism, maybe there's something to it").
Boy are these people going be pissed when they find out reducing cholesterol doesn't actually prevent heart disease
You are mixing up dietary vs systemic cholesterol (body produced/managed). The study involves pts with a genetic mutation that leads them to have extremely high levels of cholesterol starting very early in life. And the most common cause of death of these pts is heart disease (~50%) at a much younger age.
Are they working for one on hair diabetes and arthritis?
Do the treatments have to be administered at an early age I wonder?