There was a great article that I've been waiting for in the New England Journal
about antisense drugs. You know a lot of folks are gonna be saying, what the heck
is Lp(a) and maybe I don't really have any interest in that; I don't have
it. If you're thinking you don't have it, you might want to just make sure because
Lp(a) has been one of those dirty little secrets the docs didn't
share. Most docs don't even know about it, and it's a known actually well-known
cardiovascular risk. It is a variation of LDL, and it's actually an LDL, which for
some reason we can talk about a little bit later, attracts oxidized LDL. Many
people felt like we didn't have an effective treatment so the standard
response was well, you know what, we don't have anything to treat it with any drugs
or anything. So let's just not even talk about it. For example, I think it was the
Mayo cardiology medical director said well, let's just give him statins. Well
statins don't really help. Lp(a) is an issue, and it started to hit what we
call primetime. I've got several different videos on Lp(a) hitting
primetime when Bob Harper had his heart attack.
He shared, yep, it was due to Lp(a) so making a lot of progress in that
space. So that's one reason that you may want to know about it. Most of us have
never been tested for it. Another reason is the prevalence. It's really high. It's
between 20 and 40 percent depending on what you want to use for a cut point in
terms of levels. Now, we have used niacin in the past, and again, we'll get into a
little bit more about all of that as we get into that part of the presentation.
So the Lp(a), as I mentioned, Lp(a) has not been covered very well.
Again, docs felt like there wasn't much they could do for it, and so they just
didn't even test for it and didn't talk to patients about it, didn't learn about
it. And then Bob Harper had a heart attack a couple of years ago. He's on TV,
and he's celebrity known for being in shape. And
he had a heart attack. Yeah, he did, and he announced later it was due to
Lp(a). Now, what is Lp(a)? As I said before, it's something that we've
known about at least in the research areas even if the standard medical
community didn't know what to do with it. It's a variation of LDL. And if you look
at it, here's maybe the geeky part, the biochemistry part. This whole image is
what we call a lipoprotein. It is a picture of LDL. The lipoprotein is a
protein that takes cholesterol and forms it into a ball so it doesn't form a big
clot or embolus in the bloodstream, which is mostly water,
over 90%. Now, this pink reddish part represents, it's called apoB. It is the
protein that holds that cholesterol together. Now what's different about
Lp(a) from other LDL is this Kringle repeats section. It looks like the
genetics on this one got a little bit confused and created a long chain that's
hanging off. We used to think that that little chain may be actually hooked into
the endothelium. Maybe that was the cause of the inflammation. But more recently,
we're finding out something very different for some reason. This apoB
protein appears to attract and hold oxidized LDL. I know a lot of people on
our channel watch Ivor Cummins as well. Ivor Cummins has got a couple of
good videos on the importance of oxidized LDL that appears to be the bad
actor in terms of inflammation and getting in and forming plaque. So back to
that original image. How have we treated Lp(a) in the
past? As I mentioned, Mayo said we you know just give them statins. We know that
doesn't help Lp(a), but we think it'll help LDL in general. Well,
that's one way and clearly it's got his merits. The Europeans have always given
niacin. I've always given niacin. A lot of docs that I know use niacin instead.
Niacin will reliably, most reliably I'd say,
60 to 80% of the time, niacin will give us a 30% drop in
Lp(a). Again, Europeans use it. The Americans. you know just sometimes drive
me crazy as you know. Apheresis - apheresis, that's where... it's like dialysis
where you take the blood out of the body, you filter it, and you put it back in.
That does work, but it only lasts for 2 weeks, and the body makes Lp(a)
again. So that's not a great solution. Apo(a) antisense oligonucleotides. What
we're going to talk about today, that was what the New England Journal article is
about. But what is it? So here's the thing. If you go back to the genetic processes,
the process for making a protein, starts with DNA transcribed. I can't remember
the... there's some differentiate on the... anyhow, DNA is turned into a mirror RNA
image, and then the RNA image is used to translate into an amino acid sequence. So
the antisense drugs actually fit into this messenger RNA. It's going to be used
to make that amino acid protein sequence or the ApoB to make Lp(a). That
drug then is made, and it's just sort of blocks that next process. So hopefully
that helps you begin to get a little bit of understanding about what antisense
oligonucleotides means. Ao antisense means it's on the other side. It's the
mirror image. And it's an oligo, meaning a small batch. And again, it blocks that
next process. I've also done videos on where L-carnitine has been shown to help
as well. I think we can all agree unless you've got like world-class level
Lp(a), you might want to continue to focus more on things like niacin,
maybe carnitine. Because antisense drugs working very well, getting
80% impact, and that's unprecedented. I have seen one patient get an 80%
impact from niacin, and this was a patient there really you know her
Lp(a) numbers were like 70 or 80 in it. Those weren't really bad numbers. On
the other end of the spectrum, we've got folks like Joe Reilly. You remember Joe
did a video with us, maybe a couple of videos, and the highest number I've ever
seen it was like over 800, maybe over a thousand. Joe also shared with us that
he'd had the aortic valve calcification that you get with this. So again
now, that's somebody that would clearly focus on making sure that we get the
access to the oligo... on the antisense drugs as soon as possible. This is that
one of those articles on L-carnitine. Now let's get back to the New England
Journal article itself. As you see here, it was New England Journal,
January 16th of this year 2020. Lp(a) Reduction in Persons with
Cardiovascular Disease. Tsimikas is the lead author, and as I said, this is a big
deal. It's something that many of us have been waiting for quite a while. And
the methods... they just did a double-blind randomized control trial. They used
different levels different amounts - 20, 40, or 60 milligrams of the antisense drug
AKCEA-APO(a)-Lrx... you know again, no need to try to remember any of that. Up to
80% reduction. So reliably, but that was at the higher dosage levels. So
obviously, I've got a lot of patients that are very smart. They keep an eye on
this. I don't remember if it was one of my patients or Nutri Nuva somebody I've
talked with a few times out and I think... anyhow, somebody alerted me to this,
and it's again, a great article, a great development. And whoever alerted me, thank
you for letting me know. One of the reasons I don't remember is that
I've gotten emails and calls from multiple of my Lp(a)
patients. And they're all asking the same question: how can I get into the next
study? How can I get access to this? Again, it's not maybe overuse a phrase that
getting this medication is not quite ready for primetime. They're going to
need to do a little bit more work on it. And again, there's a lot of demand. One of
the things that you're going to stay happening is now, thess doctors in
standard medicine, maybe even your own cardiologist, will actually start testing
for Lp(a) because we're beginning to see we've got a treatment. Now, like
some of the other treatments like PCSK9 for example, I expect these
things are going to be maybe tens of thousands of dollars per year until the
patent breaks and/or there's significant
competition in the area. I will tell you again, the majority of my Lp(a)
patients, niacin has done a great job. So it's a great thing, it's a wonderful
thing to happen. It's gonna complicate things a little bit more because now
there's gonna be the question of okay, is this worth the new drug and its added
expense? Or do we want to continue to work with the old school stuff - niacin,
carnitine, stuff like that. Let me see if there was anything else to
cover on that. No, just mentioned the cardiovascular disease, the calcific
aortic valve stenosis which we mentioned that Joe shared with us and the comment
that the hook the crinkle repeats going into the endothelium. It's more of the
fact that for some reason, Lp(a) tends to attract oxidized LDL. Now, here
the images. Here's what happened. Again, for the higher dosages, you were getting
80% decrease with Lp(a). Really, really impressive
and unprecedented. Basically showed the impact on the other
LDL stuff like that HDL, triglycerides, As you see, very minimal impact on the
other stuff. Just focused on Lp(a). And by the way, very few side effects. The
major side effect was irritation of the injection site.
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