Thursday, July 02, 2020

Pesky PSCK9 inhibitors

For a variety of reasons I'm rather ignoring the blog at the moment. But this is too good not to post, HT to Carlos Monteiro for the link:

Serious Adverse Events and Deaths in PCSK9 Inhibitor Trials Reported on A Systematic Review

PCSK9 inhibitors do not work. However much they cost, they're useless.

This confirms (again) that the lipid hypothesis of CVD is bollocks. It was so in the 1950s. Nothing has ever changed that.

Happily only Evolocumab will kill you prematurely (with the data so far).


EDIT cavenewt emailed me this press release (see her comment for quotes). Permanent alteration of your PSCK9 gene... what could possibly go wrong? END EDIT


cavenewt said...

Why mess around with short term drugs?

"In its first tough test, CRISPR base editing slashes cholesterol levels in monkeys."

"In the seven macaques that received the PCSK9-targeting CRISPR base editor, via intravenous infusion, blood levels of the PCSK9 protein fell 89%, indicating high editing efficiency. After two weeks, the monkeys’ LDL cholesterol levels had fallen 59%...

The treatment is first aimed at people with familial hypercholesterolemia, but that might not be a big enough market:

'Verve has dreams beyond people with familial hypercholesterolemia, however. “We really do want to transform how we think about cardiovascular disease,” Kathiresan said. Instead of taking statins for decades — or, more precisely, being prescribed statins, since half of people prescribed cholesterol-lowering medications following a heart attack stop taking them within a year — people who undergo gene therapy would, if all goes well, have the same protection against heart disease as individuals with natural mutations in PCSK9, ANGPTL3, or six other protective genes in Verve’s sights.'

Peter said...

Hi cave, can't think why I didn't put the two together!!!! Edited-in a link now.

All the best, Peter

Hap said...

Apparently, since the inhibitors kill and people won't take them for very is clear that what we need is a permanent alteration in your genes. That'll do the trick.

Passthecream said...

Hap: Start warming up the lawyers now. If it turns out to be a heritable modification or just to have eg in-utero effects there will be grounds for a delightful bunch of class actions.

It fills me with wonder at how far cholesterol fanatics will go.

Eric said...

This is the NYT's reporting on the CRISPR experiment. The reporter is still totally sold on the lipid hypothesis. This is so 1990s!

Links in that article say people with that mutation don't get heart disease. Any solid proof of that? Or do they die of cancer before they can get heart disease?

From a profit angle, the jab does not look all that interesting...

Peter said...

Eric, well LMAO. Total protection based on two young adult women? The reporter and whoever informed her are deluded. Breathtakingly so!


Eric said...

Peter, I was referring to the second linked article in the linked article :)

The two women had two defective copies and were just examples that apparently, you can be healthy and reproduce with almost no LDL. The article was on people with one defective copy which results in 28% LDL reduction in blacks and 15% in whites with a different mutation that does not completely knock out the copy. Too lazy to see what these guys actually published.

Dr. Hobbs and Dr. Cohen delved into data from a study that followed blacks ages 45 to 64 for 15 years to see if they developed symptoms of heart disease.

Those who had even a single mutated gene seemed almost immune to heart disease, even though many had risk factors, including high blood pressure, diabetes and smoking.

Whites who had the less powerful mutation had a 46 percent reduction in heart disease.

Peter said...

Hi Eric,

Study is

One to think about!


Eric said...

Glad you followed up. Thanks!

ELau said...


In the review, the authors lumped data from both PCSK9is together to conclude that all-cause-mortality is not reduced and in fact increased with Evolocumab. But with the more recent paper linked below, surely Alirocumab shows a real advantage to both primary event outcomes and mortality?

ELau said...

In the article you referred to in your reply to Eric, PCSK9 mutation carriers are also at a lower risk of death from all causes. Thoughts?

Peter said...

Hi ELau, I'm unable to find all cause mortality in the paper you cite. My assumption is that it was ns increased, otherwise they would have mentioned it. I just searched on "mortality" and "death". I'm right out of ondansetron so couldn't stomach actually reading the paper in detail.

Re all cause mortality and PSCK9 genes. People with this mutation are totally and utterly protected from any attempt by the medical profession to put them on lipid lowering therapy. That's probably enough, especially in the USA where the gene shows up as protective.

If people actually know they have the gene they are also largely protected from saturophobic psychosis and vegetable oil intoxication. Especially in the USA where these last two serious illnesses are rampant.


ELau said...

Hi Peter if you click on Results it’s Table 2.

Hope you are well.

Peter said...

Thanks ELau,

We'll have to wait on that one, though it will be good enough for Marketing to take an run as it stands...