Did We Just Cure High LDL for Life?

[RetCurious]

Fascinating results from the latest gene therapy trial. The same proven platform is now being tested against triglycerides.

https://www.nejm.org/doi/full/10.1056/NEJMoa2601283

"For the first time, scientists have edited a single letter of DNA inside living people to switch off a cholesterol gene, and in the first human trial, LDL cholesterol fell by up to 62% from one infusion. This is a full, evidence-first breakdown of VERVE-102 and the Heart-2 trial: what it is, how base editing actually works, what the data does and does not prove, and why it might matter far beyond cholesterol."

View: https://www.youtube.com/watch?v=s0Sp8kM-p2o

 

[CathyGoesFar]

So freaking cool.

If I became aware of such a trial in my area I would sign up in a heartbeat. I get my first blood test since starting Repatha(also a type of PCSK9 inhibitor) and ezetimibe on Monday. Hoping for a big drop.

 

[fatbegone]

Here's a great article on cholesterol.

"For young adults in relatively good health, aggressive LDL reduction will permanently protect them from developing cardiovascular disease with nearly zero downside. Consequently, cardiovascular disease is effectively a fully solved problem."

Cardiovascular disease is a solved problem – Total Health Optimization

totalhealthoptimization.com

 

[Meritocrat]

Then, a mild rosuvastatin and ezetimibe combined use, until the gene therapy becomes more accessible, should be a good choice?

 

[lessthanhalf]

As far as I know the only currently approved and in actual use gene therapies cost millions, a very long way away from something that could be used to lower lipids. Permanent gene editing requires very strict safety evidence, errors in editing or location can cause cancers, which might be an acceptable risk in treating fatal genetic disorders, but less so for something that already has perfectly decent drug therapy, I doubt there is any realistic chance of this being a thing in the next decade even.

 

[RetCurious]

As far as I know the only currently approved and in actual use gene therapies cost millions, a very long way away from something that could be used to lower lipids. Permanent gene editing requires very strict safety evidence, errors in editing or location can cause cancers, which might be an acceptable risk in treating fatal genetic disorders, but less so for something that already has perfectly decent drug therapy, I doubt there is any realistic chance of this being a thing in the next decade even.

We may not live to see it but we do see the dawning of the hope that will drive medical research professionals.

 

[lessthanhalf]

It seems ridiculous that there are so few gene therapies actually used , when most animal studies routinely create specialised gene editing tools to knock out genes in mice or create new strains with genes missing or even knockout genes in specific tissues only or only in response to light or chemical signals. Some studies might do 10 different gene edits to test different aspects of what they are researching, and it seems very routine. There was a good Asianometry video on youtube ( great channel ) about gene therapy and why it is so expensive.

 

[UpDownLeftRightAS*]

Random, I've always had low Cholesterol levels. In the 00's I had a doc in his 80s (I was 20) tell me it was from drinking scotch and that I should eat more eggs and cheese. Ha....mabye?

The Healthy HDL is usually baseline as well. Reta knocked that down along with the other readings however, hopefully when back to a lower dose/ maintenance it will go back up as well. Would love to have HDL though the roof.

 

[RetCurious]

May I ask how long have you been on GLP-1's and your current dose?

 

[psycho_driver]

Random, I've always had low Cholesterol levels. In the 00's I had a doc in his 80s (I was 20) tell me it was from drinking scotch and that I should eat more eggs and cheese. Ha....mabye?

The Healthy HDL is usually baseline as well. Reta knocked that down along with the other readings however, hopefully when back to a lower dose/ maintenance it will go back up as well. Would love to have HDL though the roof.

HDL of above 75 or so seem to have diminishing returns and there have been some links shown between abnormally high HDL and vulnerability to dementia later in life. It's like practically everything else; too much or too little of it is bad. I was just going over my wife's bloodwork and a couple of years ago she had an HDL result of 120. Most recent was 90. Mine, meanwhile, sits in the low 30s. We eat pretty much the same diet.

I can't help but think that this gene editing approach will have consequences down the road for these patients. There could quite possibly be a reason they're genetically predisposed to have higher cholesterol. I hope I'm wrong. Also, I've heard from people I generally tend to trust that lowering cholesterol through interventions such as statins doesn't save you from a future heart attack, it just postpones it. There are multiple factors that lead up to plaque build up. If you have high cholesterol but consistently low inflammation then your risk is reduced quite a bit. Keeping your circulating calcium from getting too high will also be protective (take k2 with your d3!).

 

[UpDownLeftRightAS*]

HDL of above 75 or so seem to have diminishing returns and there have been some links shown between abnormally high HDL and vulnerability to dementia later in life. It's like practically everything else; too much or too little of it is bad. I was just going over my wife's bloodwork and a couple of years ago she had an HDL result of 120. Most recent was 90. Mine, meanwhile, sits in the low 30s. We eat pretty much the same diet.

I can't help but think that this gene editing approach will have consequences down the road for these patients. There could quite possibly be a reason they're genetically predisposed to have higher cholesterol. I hope I'm wrong. Also, I've heard from people I generally tend to trust that lowering cholesterol through interventions such as statins doesn't save you from a future heart attack, it just postpones it. There are multiple factors that lead up to plaque build up. If you have high cholesterol but consistently low inflammation then your risk is reduced quite a bit. Keeping your circulating calcium from getting too high will also be protective (take k2 with your d3!).

Very good points all around. Our biological tuning is unique to each of us, and it's remarkable how many interconnected systems are constantly working together to maintain balance. When we intervene with drugs, gene editing, or other therapies, we often focus on the primary outcomes, but there are countless downstream effects that we're still learning to understand.

That said, I find the science incredibly exciting. The fact that we're beginning to identify, modify, and potentially correct genetic pathways that influence disease would have seemed like science fiction not long ago. There will undoubtedly be surprises along the way, both positive and negative, but that's how progress has always worked.

In many ways, we're still in the early stages of understanding the complexity of human biology. We've learned a tremendous amount, but there is still so much we don't know about the deeper mechanisms that govern health, aging, and disease.

 

[CathyGoesFar]

I can't help but think that this gene editing approach will have consequences down the road for these patients. There could quite possibly be a reason they're genetically predisposed to have higher cholesterol. I hope I'm wrong.

You are very wrong that there is any biological benefit to having higher cholesterol. People with familial hypercholesterolemia have heart attacks and die if not treated. 50% of men and 30% of women have a heart attack prior to the age of 60. My own mother was only 39 years old when she died of a heart attack. Nature doesn't always get it right. My "high score" of 400+ total cholesterol was measured while I was a fit active 21 year old soldier eating a decent diet.