Two Docs Talk: Lp(a) Trailer

Be a part of advancing science by participating in clinical research.

Have a question for Dr. Koren? Email him at askDrKoren@MedEvidence.com

Listen on Spotify
Listen on Apple Podcasts
Watch on YouTube

Share with a friend. Rate, Review, and Subscribe to the MedEvidence! podcast to be notified when new episodes are released.

Follow us on Social Media:
Facebook
Instagram
X (Formerly Twitter)
LinkedIn

Want to learn more? Checkout our entire library of podcasts, videos, articles and presentations at www.MedEvidence.com

Music: Storyblocks - Corporate Inspired

Thank you for listening!

Chapters

• 0:00 Introduction to LP(a) Issues
• 0:26 Dr. Leahy's Personal LP(a) Story
• 1:47 Chest Pain While Surfing
• 4:09 Treatment with ASO Technology
• 6:34 The Importance of LP(a) Testing
• 7:57 Next Steps in LP(a) Research

Transcript

SPEAKER_00: 0:00

LPA issues are fundamentally a little bit different than cholesterol issues. My name is Dr. Michael Korn, and I'm delighted to moderate another session of MedEvidence. And we're very fortunate today to have a special guest, Dr. Dennis Leahy from San Diego, who's going to talk about lipoprotein little A from both the perspective of a clinical cardiologist, interventional cardiologist, and also a patient that has this problem.

SPEAKER_01: 0:26

I'm a classic LP little A person in that I had a very strong family history of vascular disease.

SPEAKER_00: 0:32

Probably came mostly from my mother's side of the family. This family history concept is really, really important. So going back to my cardiology days, one of the things that struck me when I first learned about LPA is the really, really strong family history of people with this problem. So you'll you'll get folks, for example, that have a father and mother who had some complications in their 20s, 30s, or 40s. And this is following each generation down the road. So uh, and and to that point, uh I I did my training at New York Hospital, and one of the famous LPA patients at New York Hospital was Arthur Ash, who had this type of family history of having both mother and father have heart disease at a young age, and you know, Arthur Ash, as a fit professional athlete, had his first cardiac issue at age 29. So it was a very profound introduction to me of this particular problem.

SPEAKER_01: 1:27

So uh in 2002, you'll probably recall, um LP little A was it was known. I mean, it's been known as a as a as a lipid particle for some time, but uh there's a real struggle to figure out whether it's strictly a biomarker or causative agent for vascular disease. And in 2002, things were every bit as murky as they were before that. But um I was kind of a typical LP little A patient and remain so in that if you look at me and you looked at 10 other people in the room, you'd say, who's the last guy here to get vascular disease? And it would probably be me. I've always been very fit. I've exercised uh all my life uh and had other virtually no other risk factors.

SPEAKER_00: 2:06

Just for the audience, LPA is measured in different ways. In fact, there's kind of a debate of the best way to measure it. But the the two major ways of measuring it are either by mass, and the typical measurement there is milligrams per deciliter, or by concentration, and then the typical measurement would be nanomoles per liter. And they are related to each other, but because L uh because lipoprotein little A is a heterogeneous molecule, more and more of us think that the concentration is a better way to describe it, because each particle can actually have a different mass, and it's hard to know your risk based on quote the size of your particles. So just looking at the overall concentration of particles is probably the way most of us are going in the lipid field.

SPEAKER_01: 2:55

So, anyway, um I was uh doing my usual thing, and then a very uh important moment in my life was uh New Year's morning on uh 2007. So this is about four years after I had my my uh negative calcium scan. I was surfing. Uh it was a cold, windy morning for San Diego and uh kind of an arduous paddle out. And I had my first episode of chest pain when I was paddling out, and I knew exactly what it was uh having been uh in this position with thousands of patients over the years. Kind of backed off and uh and got into the beach, the the pain was gone, but I was quite certain uh I was just I was now living out my my legacy here as a leahy. And in indeed, so then I I did get a cardiac workup uh and uh had some stents placed shortly thereafter. Uh three months after my stent procedure, I was surfing, same beach, same situation, had chest pain again.

SPEAKER_00: 3:53

Was that your is that is that standard cardiac rehab in San Diego is surfing? It is it is for me.

SPEAKER_01: 3:59

Uh and so sure enough, uh I had rhiztenosis in in one of the stents. Um the other one didn't look too bad at that time, and we decided to stent within the stent with a different uh a different coating. These were drug-alluding stents. Never had any issues with blood pressure, always at ideal weight, um, no diabetes, uh never smoker. It was all it was pretty much LP delay, and then perhaps not perfectly ideal LDL, as I said with my 2002 readings. Part of the part of the good fortune of my story, I guess the bad fortune is I have this problem, but the good fortune is I've had access to world-class healthcare, and that's really gotten me through all this Zionis pharmaceuticals, where they have developed this um ASO or anti-sense oligonucleotide treatment for LP Lelay, which is a is a gene-slowing approach to try to suppress LP Lelay production. Uh they'd had one successful phase two trial and they were starting another one. And it sounded like a great option because, unlike other trials where it's frequently a 50-50 chance of getting active treatment, this was a dosing trial, so I had a five out of six chance of actually being on an active drug. So I was in that in that study for one year uh with, as you know, successful and impressive suppression of LP delay production. Um with a uh I I think I was on a uh once every two-week injection, subcutaneous injection. Uh very simple procedure, which has been shown to be quite safe with uh minimal side effects.

SPEAKER_00: 5:32

And this is the uh the molecule that we call pelicarsin now, is that correct? Right. Right. And yeah, antisense oligonucleotide that actually prevents the the production of the protein that is essential for the assembly of lipoprotein lay right outside the nucleus of the of the hepatocytes. So um that's a fascinating technology and really, really exciting. And um so exciting that as I understand it, Novartis uh bought the product.

SPEAKER_01: 6:02

Right. You know, Novartis, of course, is in hopefully towards the end of a trial, a major, major trial that will be a really uh, you know, really a landmark uh kind of pivotal trial of whether whether these things are going to result in lower incidence of cardiovascular events by suppressing LP little A production. The the thing that I have actually written a couple pieces on that have been uh kind of op-eds that have have gotten on a couple online sites is I feel uh very passionate that everyone in the world should be tested for their LP little A level. I think it's an extremely important part of where we're going with LP little A. I don't want to get too far in the weeds if if this is this is not something you want to pursue, but you only need to be tested once to be essentially to stratify your risk because the level doesn't change much uh from age five onwards. Your LP little A level is going to be your LP little A level. Well, LP little A has kind of suffered uh uh a weird history in that it really hasn't ever gotten the attention it deserves, even though I think particularly the past decade, the elegant research that you and other people have been involved in have really clarified its role and given a direction to how we should treat it. But that is not translated well in the clinical world. You you talk to the average doctor on the street and ask them about LP delay, and they're still kind of mystified. And part of the reason for that is it was always thought to be non-modifiable, but now we know it is modifiable and probably safely so.

SPEAKER_00: 7:30

Getting a little technical, um the the trials that we're doing now here that we are enrolling for involves something called small interfering RNA, which is another, quote, genetically based way of preventing the assembly of lipoprotein little A. And it involves something called the RNA-induced silencing complex, which is part of all the cells that's actually trained to look for pieces of genetic material that can cause problems. It's a sort of an intrinsic mechanism of cells to prevent viruses from doing damage. So they're looking for so sort of bad pieces of genetic material. And we can train these parts of the cells to identify the strands that are important for making lipoprotein linol A. And with this technology, it seems incredibly safe so far. We're able to reduce levels of LPA by up to 95%, as mentioned. So the next step is to see whether that huge reduction in LPA will translate into fewer heart attacks and strokes for people at extremely high risk.