Edits To a Cholesterol Gene Could Stop the Biggest Killer On Earth (technologyreview.com) 69
A volunteer in New Zealand has become the first person to undergo DNA editing in order to lower their blood cholesterol, a step that may foreshadow wide use of the technology to prevent heart attacks. MIT Technology Review reports: The experiment, part of a clinical trial by the US biotechnology company Verve Therapeutics, involved injecting a version of the gene-editing tool CRISPR in order to modify a single letter of DNA in the patient's liver cells. According to the company, that tiny edit should be enough to permanently lower a person's levels of "bad" LDL cholesterol, the fatty molecule that causes arteries to clog and harden with time. The patient in New Zealand had an inherited risk for extra-high cholesterol and was already suffering from heart disease. However, the company believes the same technique could eventually be used on millions of people in order to prevent cardiovascular disease.
In New Zealand, where Verve's clinical trial is taking place, doctors will give the gene treatment to 40 people who have an inherited form of high cholesterol known as familial hypercholesterolemia, or FH. People with FH can have cholesterol readings twice the average, even as children. Many learn they have a problem only when they get hit with a heart attack, often at a young age. The study also marks an early use of base editing, a novel adaptation of CRISPR that was first developed in 2016. Unlike traditional CRISPR, which cuts a gene, base editing substitutes a single letter of DNA for another.
The gene Verve is editing is called PCSK9. It has a big role in maintaining LDL levels and the company says its treatment will turn the gene off by introducing a one-letter misspelling. [...] One reason Verve's base-editing technique is moving fast is that the technology is substantially similar to mRNA vaccines for covid-19. Just like the vaccines, the treatment consists of genetic instructions wrapped in a nanoparticle, which ferries everything into a cell. While the vaccine instructs cells to make a component of the SARS-CoV-2 virus, the particles in Verve's treatment carry RNA directions for a cell to assemble and aim a base-editing protein, which then modifies that cell's copy of PCSK9, introducing the tiny mistake. In experiments on monkeys, Verve found that the treatment lowered bad cholesterol by 60%. The effect has lasted more than a year in the animals and could well be permanent. The report notes that the human experiment does carry some risk. "Nanoparticles are somewhat toxic, and there have been reports of side effects, like muscle pain, in people taking other drugs to lower PCSK9," reports MIT Technology Review. "And whereas treatment with ordinary drugs can be discontinued if problems come up, there's as yet no plan to undo gene editing once it's performed."
In New Zealand, where Verve's clinical trial is taking place, doctors will give the gene treatment to 40 people who have an inherited form of high cholesterol known as familial hypercholesterolemia, or FH. People with FH can have cholesterol readings twice the average, even as children. Many learn they have a problem only when they get hit with a heart attack, often at a young age. The study also marks an early use of base editing, a novel adaptation of CRISPR that was first developed in 2016. Unlike traditional CRISPR, which cuts a gene, base editing substitutes a single letter of DNA for another.
The gene Verve is editing is called PCSK9. It has a big role in maintaining LDL levels and the company says its treatment will turn the gene off by introducing a one-letter misspelling. [...] One reason Verve's base-editing technique is moving fast is that the technology is substantially similar to mRNA vaccines for covid-19. Just like the vaccines, the treatment consists of genetic instructions wrapped in a nanoparticle, which ferries everything into a cell. While the vaccine instructs cells to make a component of the SARS-CoV-2 virus, the particles in Verve's treatment carry RNA directions for a cell to assemble and aim a base-editing protein, which then modifies that cell's copy of PCSK9, introducing the tiny mistake. In experiments on monkeys, Verve found that the treatment lowered bad cholesterol by 60%. The effect has lasted more than a year in the animals and could well be permanent. The report notes that the human experiment does carry some risk. "Nanoparticles are somewhat toxic, and there have been reports of side effects, like muscle pain, in people taking other drugs to lower PCSK9," reports MIT Technology Review. "And whereas treatment with ordinary drugs can be discontinued if problems come up, there's as yet no plan to undo gene editing once it's performed."
Curious to see how it pans out (Score:1, Interesting)
Re: (Score:1, Flamebait)
Is ivermectin still a thing? Any other cheap drugs available at Tractor Supply?
Re:Curious to see how it pans out (Score:5, Interesting)
More seriously, it takes at least (maybe a lot more) say, 150 years or say, ~2.5 human generations to evaluate the side effects of manipulating DNA. It might be a lot less with organism having a shorter life span thus shorter generations period but then again, we can't be sure humans would react the same way to such modification.
Re:Curious to see how it pans out (Score:5, Insightful)
There's no germ line editing here, so generations aren't particularly any more involved than with any other source of mutation in somatic cells.
You aren't going to pass on changes from editing some of the cells in your liver, and the likelihood of this reaching gametes in a functional form is extremely low. It'll actually be harder to apply this technique anywhere _except_ your liver, given that your liver is where this kind of thing goes to get removed, but in this case that's where the target is already.
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Unless the patient is a "birthing person" and gives birth to a sibling after receiving the treatment.
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Babies don't come from livers...
Google "where do babies come from" and go from there.
Maybe don't do it at work though. Or near any Christian Conservatives.
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Unless the patient is a "birthing person" and gives birth to a sibling after receiving the treatment.
If you're giving birth to your own sibling... You probably have bigger problems anyway.
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Unless the patient is a "birthing person" and gives birth to a sibling after receiving the treatment.
If you're giving birth to your own sibling... You probably have bigger problems anyway.
There's certainly a higher rate of genetic disease that way.
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This drives me nuts (Score:4, Funny)
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This is the kind of stuff that drives me nuts. The future is so close... and yet so far.
The present, by its very definition is a gift... yet the future is now.
We're nearly to the point of monetizing the art of curing cancer.
Cholesterol Gene, you say (Score:2)
Well, that's at least promising, considering the lengthening of the telomerase we expect from you shortly.
TL;DR (Score:2, Funny)
Cyclodextrin (Score:3)
How about this gene-editing, plus cyclodextrin? Reference on cyclodextrin: https://www.ncbi.nlm.nih.gov/p... [nih.gov]
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How about this gene-editing, plus cyclodextrin? Reference on cyclodextrin: https://www.ncbi.nlm.nih.gov/p... [nih.gov]
How about losing your hearing [nih.gov] as a result of cyclodextrin's ototoxicity [nih.gov]?
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I don't think dead people hear very well either.
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First, it's better to be deaf or hard of hearing than dead or vegetablized due to a stroke. Second, that study pumped those mice with massive doses of cyclodextrin, dosages when scaled up proportional to human body weight, nobody sane would take.
why not treat the underlying issue instead? (Score:2)
Cholesterol doesn't just build up for no reason. It's because the arteries are unhealthy.
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Yeah good idea .. don't eat anything with cholesterol. Eat raw sugar and water.
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Note, any food that is plant or animal .. contains the nasty chemical pantothenic acid, from which your body can synthesize the nefarious compound known as Coenzyme A. Then, by surreptitiously acetylating its stash of Coenzyme A and adding some very toxic chemicals.. the body can cook itself cholesterol to get high off of.. at which point you're fucked. That's why I recommend a strict diet of sugar + water. The only way to avoid evil cholesterol molecules.
Re:why not treat the underlying issue instead? (Score:5, Informative)
Yeah good idea .. don't eat anything with cholesterol. Eat raw sugar and water.
Many articles have noted research indicating that cholesterol in food doesn't affect cholesterol in the blood as much as previously thought. From Why You Should No Longer Worry About Cholesterol in Food [clevelandclinic.org] and Why Dietary Cholesterol Does Not Matter (For Most People) [healthline.com] (and others):
High levels of “bad” cholesterol in the blood, which have been linked to heart disease, are still a health concern.
But evidence shows people no longer have to be concerned about eating foods that are high in cholesterol. What’s changed is that many researchers and physicians believe that eating cholesterol-rich foods such as eggs may not affect the cholesterol that is in your blood.
“Your genetic makeup – not diet – is the driving force behind cholesterol levels, says Dr. Nissen. “The body creates cholesterol in amounts much larger than what you can eat, so avoiding foods that are high in cholesterol won’t affect your blood cholesterol levels very much.”
About 85% of the cholesterol in the circulation is manufactured by the body in the liver. It isn’t coming directly from the cholesterol that you eat, according to Dr. Nissen.
The greater danger for everyone is in foods that are high in trans fats.
Re:why not treat the underlying issue instead? (Score:5, Informative)
Adding injury to insult, the cholesterol panic lead many people to switch to trans fat laden margarine in the late '70s.
Then people went with low fat processed foods that had heaps of sugar and salt in them to make up for fat free foods tasting like wet cardboard otherwise. And the lack of fat made sure they ate plenty of it.
And for the cherry on top, fat shamers would jeer any overweight person that dared to eat anything that might have been stored within 10 meters of fat, helping to further perpetuate the problem.
Re:why not treat the underlying issue instead? (Score:5, Informative)
Yeah good idea .. don't eat anything with cholesterol. Eat raw sugar and water.
Many articles have noted research indicating that cholesterol in food doesn't affect cholesterol in the blood as much as previously thought. From Why You Should No Longer Worry About Cholesterol in Food [clevelandclinic.org] and Why Dietary Cholesterol Does Not Matter (For Most People) [healthline.com] (and others):
High levels of “bad” cholesterol in the blood, which have been linked to heart disease, are still a health concern.
But evidence shows people no longer have to be concerned about eating foods that are high in cholesterol. What’s changed is that many researchers and physicians believe that eating cholesterol-rich foods such as eggs may not affect the cholesterol that is in your blood.
“Your genetic makeup – not diet – is the driving force behind cholesterol levels, says Dr. Nissen. “The body creates cholesterol in amounts much larger than what you can eat, so avoiding foods that are high in cholesterol won’t affect your blood cholesterol levels very much.”
About 85% of the cholesterol in the circulation is manufactured by the body in the liver. It isn’t coming directly from the cholesterol that you eat, according to Dr. Nissen.
The greater danger for everyone is in foods that are high in trans fats.
Actually, all you have to do is look at the problem from an engineering perspective. That is: what is the *purpose* of LDL cholesterol, *why* does your body make it? And the answer is: LDL particles are made by your liver, it is how your liver exports excess energy to other body parts. So, how does your liver end up with excess energy? And here the answer is, because of sugar. High levels of glucose in blood are quite toxic [wikipedia.org], so when you eat that donut your liver basically has to scoop up all that excess sugar from your bloodstream, whether it needs it or not. So now it has excess energy. Some of it gets stored as glycogen, most of it gets converted into fats, wrapped into LDL and pushed back into bloodstream for reuptake in fatty tissue.
Of course there's has so many things that can get overloaded in this process. If your liver fails to scoop up the sugar you get diabetes. If there's a problem with with the "wrapping up in LDL" part then the fat stays in the liver and you get nonalcoholic fatty liver disease (and I bet this is going to be the problem with this treatment). If your fatty tissue has problems with uptake of the LDL (as in most men for example) then it stays in bloodstream and hammers your arteries (that's why women tend to just get obese, while men tend to stay leaner and then die of heart attacks).
Also note that when you eat fats or proteins it doesn't happen - neither of those are toxic and need to be scooped up by the liver, so the body just deals with both of them at a leisure, without LDL being involved.
So of course the way to fix it is - surprisingly - low carb diet. No liver overload, no LDL. And it happens quite quickly - if you're not convinced then do a low carb (but I mean, *low* carb, like under 30 grams of sugar+starch daily) for just 5 days and do your lipidogram. I guarantee you'll get best numbers in your life. And I mean, even if I'm wrong, 5 days won't kill you, right?
Re:why not treat the underlying issue instead? (Score:5, Interesting)
However, the hospitals are working on outdated ideas, promoting lower fat, low salt but absolutely no advice on sugar. Ever wondered why diabetics are twice as likely to have heart disease?
It isn't because they eat high fat, high salt diets compared to the rest of the population, it their inability to control sugar. Too much sugar is what is causing obesity, diabetes and heart disease. If there is one health message that should be promoted, it should be keep your sugar intake low.
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when i did the nuts and plant based diet my numbers were cut in half dramatically. no sugar
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What's really crazy is how if you are in the hospital eating their food it is mostly processed high-carb crap
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The present guidelines are probably still under the influence of a corrupt USDA director that previously had accepted money from the sugar industry. The resulting research surprisingly played down the effect of sugar and blamed fat for the rising cardiovascular health problems.
"The Harvard scientists and the sugar executives with whom they collaborated are no longer alive. One of the scientists who was paid by the sugar industry was D. Mark Hegsted, who went on to become the head of nutrition at the United
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LDL particles are made by your liver, it is how your liver exports excess energy to other body parts.
What? This isn't even right. LDL cholesterol is how your liver sends cholesterol to all parts of your body.
Why does your body need cholesterol? It is a part of the cell walls in all your cells. It is extremely necessary.
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LDL particles are made by your liver, it is how your liver exports excess energy to other body parts.
What? This isn't even right. LDL cholesterol is how your liver sends cholesterol to all parts of your body.
Why does your body need cholesterol? It is a part of the cell walls in all your cells. It is extremely necessary.
Yes, that is the other function of LDL. Don't worry, a low carb diet won't interfere with that, pretty much the only way to interfere with that is to over-medicate. And yes, what I said is a simplification, neglecting VLDL, HDL, and all the others.
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From here: https://nutritionfacts.org/vid... [nutritionfacts.org]
How do we know excess dietary fat is bad? Because it’s been put to the test. Randomize people to the same low-calorie diet, but one that’s low-fat versus one that’s high-fat, and within just two weeks, the low-fat diet decreased liver fat by 20 percent, whereas the same number of calories on a high-fat diet increased liver fat by 35 percent!
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So, one of those Egg Council creeps got to you too, huh?
Re:why not treat the underlying issue instead? (Score:4, Informative)
Cholesterol doesn't just build up for no reason. It's because the arteries are unhealthy.
Yup, cholesterol is important for tissue repair and (apparently) repairs micro fractures in the blood vessel walls and also Cholesterol Plays an Important Role in Myelin Regeneration [technologynetworks.com]. The problem of build-up on blood vessel seems to come from continued damage and repair ... From What is Cholesterol and What Does it Do to Your Body? [sunshineclinic.org] (emphasis mine) :
Cholesterol is not always bad. It becomes harmful when inflammation in your arteries occurs. These inflammations can cause holes in the artery walls. Cholesterol in your bloodstream reacts to the affected area and immediately tries to repair the damage. As it works to heal the artery; bad cholesterol, pile up, and thicken arterial walls causing calcification. This build-up narrows blood passages causing pressure to the damaged arterial walls, which can then lead to ruptures.
From Why Is Cholesterol Needed by the Body? [healthline.com]
In our bodies, cholesterol serves three main purposes:
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Indeed. Cholesterol is essential to the health of anyone. It's involved in the synthesis of our hormones, cell membranes, bile acids, and nutrients like vitamin D. Both LDL and HDL are essential.
The danger with cholesterol is if it oxidises. Then your immune system attacks it, causing inflammation, which then attracts blood platelets to build up (normal reaction to try and stop bleeding), and you then have a blockage.
So, try to avoid eating oxidised cholesterol. Reduce or avoid refined foods and sugars
Re: why not treat the underlying issue instead? (Score:1, Flamebait)
Re: why not treat the underlying issue instead? (Score:2)
As per the article:
"The patient in New Zealand had an inherited risk for extra-high cholesterol and was already suffering from heart disease."
So the underlying issue is that this person had an inherited risk, buried their DNA. In essence, this approach *is* treating the underlying issue by altering their DNA.
One thing that I don't see in the article: is the gene they're editing the one that's flawed in the first place? Are they essentially correcting the inherited error, or introducing a new error that off
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Re:COVID (Score:5, Insightful)
Well, in the case of the covid vaccine it doesn't include any of the machinery this includes to do a DNA edit and just has the code for a spike protein, and in this case, it's got a whole payload of machinery attempting to do a permanent modification to a patch of the patient's tissue in their liver, so yes, it's rather different situations. What we don't know is stuff like whether the modified liver cells will be dividing and persisting or whether they'll be replaced by fresh, unmodified cells off a stem line, that kind of thing.
It's only "similar" in that they both use RNA and a delivery mechanism, it differs in every other detail, and the "with RNA" has barely more information than tacking on "with a computer".
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Also, presumably both use modRNA to prevent reverse-transcription, so the only way that you'd get DNA changes is if the RNA contains explicit coding to splice the DNA.
Re:COVID (Score:5, Insightful)
Tel me again how the COVID vaccine doesn't alter DNA?
What would be the point? You obviously didn't understand it the first twenty times.
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You know what they say, you can lead a jackass to water but you can't make him think.
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As soon as I read the article summary I thought this is a real face-palm moment, to mention how this method is similar to mRNA vaccines, and that this method actually does explicitly alter DNA in an irreversible way. Talk about feeding the trolls!
Already sent my request to join the study. (Score:5, Informative)
I'm a (relatively) healthy individual that went in a few years back for my first cholesterol test (yeah, I should have done it ages ago), since I was well into my 40s. I figured I eat healthy, I exercise a lot, I was in great shape!
My fasting lipid panel was ~600, with the lions share being LDL. Turns out I have multiple mutations and FH was probably going to kill me sooner, rather than later.
They ran me through the treadmill tests, which I passed with flying colors (yay all that exercise), so I wasn't going to stroke out in the next month or so.
So now I'm on a regimen of rosuvastatin, ezetimibe, and injections of evolocumab, all of that to get my cholesterol to healthy levels, when I was already sticking to a mostly plant diet, no red meat, etc. My body just has zero capacity to even deal with the cholesterol it naturally produces, so it will remain sky-high unless I am constantly taking meds AND eating healthy.
So something like this would be AMAZING, even if it just meant I could stop giving myself shots, because I could actually GO somewhere on vacation and not have to bring refrigerated meds along with.
Plus, they might screw up and give me the ability to see in the dark.
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That sucks...genes can be such a nuisance.
Curious if you or your health professionals considered that you may just have abnormally high LDL? There are so many variations of 'healthy', some people have really low iron, for example, but seem to be fine, without any of the typical effects of low-iron.
Of course it's something to be wary of - have you done any tests to detect any blockage, or if cholesterol is actually accumulating anywhere?
I'm most definitely not a doctor or giving any advice, just curious.
Re:Already sent my request to join the study. (Score:4, Interesting)
That sucks...genes can be such a nuisance.
Curious if you or your health professionals considered that you may just have abnormally high LDL? There are so many variations of 'healthy', some people have really low iron, for example, but seem to be fine, without any of the typical effects of low-iron.
Of course it's something to be wary of - have you done any tests to detect any blockage, or if cholesterol is actually accumulating anywhere?
I'm most definitely not a doctor or giving any advice, just curious.
Genetic testing shows a few mutations, one problem is that my liver basically has no receptors for removal of excess cholesterol. Statins will work to increase that number in most folks, but for me it only makes a small difference. So another med works to stop reabsorption in my digestive tract, so more is removed via that path. Still not enough, so the shot works as an antibody of sorts, which does the final trick to get things to a normal level.
Testing was done an everything seemed ok on the tests in terms of blockages, but I *DO* have cholesterol deposits on my knuckles, knees, etc. So it does build up.
Oddly the way this was discovered was going in for an eye exam, and the doc noticed a heavy cholesterol ring around my iris, that is what started the whole process moving forward.
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Ahh nuts, that's harsh, glad you caught it, thanks for sharing and hope you keep it under control!
Edits to fix undesirable appearance (Score:1)
Stop "Biggest Killer On Earth"? (Score:2)
Humans?
Bacteria?
Stupidity?
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Its blue whales. They ***each*** eat up to 32000 lbs of organisms ***per day***. They are death.
False Assertion (Score:2)
Cholesterol is not the biggest killer on earth.
That's a lie.
Air Pollution is the biggest killer on earth.
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Air pollution is currently considered the fourth biggest killer on earth. Some claim that this methodology ignores certain contributing factors that are under-estimated. That is, air pollution does increase the chance of a heart attacks, accounting for 5 million of the 9 million deaths attributed to Air Pollution. But some people think the 5 million # should be higher.
Biggest by far (Score:2)
Edits To a Cholesterol Gene Could Stop the Biggest Killer On Earth
Dictatorship, massive corruption, and general lack of freedom?
Doesn't seem likely, but I'll bite.
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Its blue whales. They ***each*** eat up to 32000 lbs of organisms ***per day***. They are death.
In the mean time... (Score:2)
You should filter your coffee with a paper filter to remove the LDL-cholesterol-increasing cafestol:
https://www.ncbi.nlm.nih.gov/p... [nih.gov]