September 26, 2025 • 8 mins
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
SPEAKER_00 (00:00):
LPA issues are fundamentally a little bit
different than cholesterolissues.
My name is Dr.
Michael Korn, and I'm delightedto moderate another session of
MedEvidence.
And we're very fortunate todayto have a special guest, Dr.
Dennis Leahy from San Diego,who's going to talk about
lipoprotein little A from boththe perspective of a clinical
(00:21):
cardiologist, interventionalcardiologist, and also a patient
that has this problem.
SPEAKER_01 (00:26):
I'm a classic LP little A person in that I had a
very strong family history ofvascular disease.
SPEAKER_00 (00:32):
Probably came mostly from my mother's side of the
family.
This family history concept isreally, really important.
So going back to my cardiologydays, one of the things that
struck me when I first learnedabout LPA is the really, really
strong family history of peoplewith this problem.
So you'll you'll get folks, forexample, that have a father and
mother who had somecomplications in their 20s, 30s,
(00:54):
or 40s.
And this is following eachgeneration down the road.
So uh, and and to that point, uhI I did my training at New York
Hospital, and one of the famousLPA patients at New York
Hospital was Arthur Ash, who hadthis type of family history of
having both mother and fatherhave heart disease at a young
(01:15):
age, and you know, Arthur Ash,as a fit professional athlete,
had his first cardiac issue atage 29.
So it was a very profoundintroduction to me of this
particular problem.
SPEAKER_01 (01:27):
So uh in 2002, you'll probably recall, um LP
little A was it was known.
I mean, it's been known as a asa as a lipid particle for some
time, but uh there's a realstruggle to figure out whether
it's strictly a biomarker orcausative agent for vascular
disease.
And in 2002, things were everybit as murky as they were before
(01:47):
that.
But um I was kind of a typicalLP little A patient and remain
so in that if you look at me andyou looked at 10 other people in
the room, you'd say, who's thelast 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 uhand had other virtually no other
risk factors.
SPEAKER_00 (02:06):
Just for the audience, LPA is measured in
different ways.
In fact, there's kind of adebate of the best way to
measure it.
But the the two major ways ofmeasuring it are either by mass,
and the typical measurementthere is milligrams per
deciliter, or by concentration,and then the typical measurement
would be nanomoles per liter.
(02:27):
And they are related to eachother, but because L uh because
lipoprotein little A is aheterogeneous molecule, more and
more of us think that theconcentration is a better way to
describe it, because eachparticle can actually have a
different mass, and it's hard toknow your risk based on quote
the size of your particles.
(02:48):
So just looking at the overallconcentration of particles is
probably the way most of us aregoing in the lipid field.
SPEAKER_01 (02:55):
So, anyway, um I was uh doing my usual thing, and
then a very uh important momentin my life was uh New Year's
morning on uh 2007.
So this is about four yearsafter I had my my uh negative
calcium scan.
I was surfing.
Uh it was a cold, windy morningfor San Diego and uh kind of an
arduous paddle out.
(03:15):
And I had my first episode ofchest pain when I was paddling
out, and I knew exactly what itwas uh having been uh in this
position with thousands ofpatients over the years.
Kind of backed off and uh andgot into the beach, the the pain
was gone, but I was quitecertain uh I was just I was now
living out my my legacy here asa leahy.
(03:38):
And in indeed, so then I I didget a cardiac workup uh and uh
had some stents placed shortlythereafter.
Uh three months after my stentprocedure, I was surfing, same
beach, same situation, had chestpain again.
SPEAKER_00 (03:53):
Was that your is that is that standard cardiac
rehab in San Diego is surfing?
It is it is for me.
SPEAKER_01 (03:59):
Uh and so sure enough, uh I had rhiztenosis in
in one of the stents.
Um the other one didn't look toobad at that time, and we decided
to stent within the stent with adifferent uh a different
coating.
These were drug-alluding stents.
Never had any issues with bloodpressure, always at ideal
weight, um, no diabetes, uhnever smoker.
(04:22):
It was all it was pretty much LPdelay, and then perhaps not
perfectly ideal LDL, as I saidwith my 2002 readings.
Part of the part of the goodfortune of my story, I guess the
bad fortune is I have thisproblem, but the good fortune is
I've had access to world-classhealthcare, and that's really
gotten me through all thisZionis pharmaceuticals, where
they have developed this um ASOor anti-sense oligonucleotide
(04:45):
treatment for LP Lelay, which isa is a gene-slowing approach to
try to suppress LP Lelayproduction.
Uh they'd had one successfulphase two trial and they were
starting another one.
And it sounded like a greatoption because, unlike other
trials where it's frequently a50-50 chance of getting active
treatment, this was a dosingtrial, so I had a five out of
(05:05):
six chance of actually being onan active drug.
So I was in that in that studyfor one year uh with, as you
know, successful and impressivesuppression of LP delay
production.
Um with a uh I I think I was ona uh once every two-week
injection, subcutaneousinjection.
Uh very simple procedure, whichhas been shown to be quite safe
(05:29):
with uh minimal side effects.
SPEAKER_00 (05:32):
And this is the uh the molecule that we call
pelicarsin now, is that correct?
Right.
Right.
And yeah, antisenseoligonucleotide that actually
prevents the the production ofthe protein that is essential
for the assembly of lipoproteinlay right outside the nucleus of
the of the hepatocytes.
(05:52):
So um that's a fascinatingtechnology and really, really
exciting.
And um so exciting that as Iunderstand it, Novartis uh
bought the product.
SPEAKER_01 (06:02):
Right.
You know, Novartis, of course,is in hopefully towards the end
of a trial, a major, major trialthat will be a really uh, you
know, really a landmark uh kindof pivotal trial of whether
whether these things are goingto result in lower incidence of
cardiovascular events bysuppressing LP little A
production.
The the thing that I haveactually written a couple pieces
(06:23):
on that have been uh kind ofop-eds that have have gotten on
a couple online sites is I feeluh very passionate that everyone
in the world should be testedfor their LP little A level.
I think it's an extremelyimportant part of where we're
going with LP little A.
I don't want to get too far inthe weeds if if this is this is
not something you want topursue, but you only need to be
(06:45):
tested once to be essentially tostratify your risk because the
level doesn't change much uhfrom age five onwards.
Your LP little A level is goingto be your LP little A level.
Well, LP little A has kind ofsuffered uh uh a weird history
in that it really hasn't evergotten the attention it
deserves, even though I thinkparticularly the past decade,
(07:06):
the elegant research that youand other people have been
involved in have reallyclarified its role and given a
direction to how we should treatit.
But that is not translated wellin the clinical world.
You you talk to the averagedoctor on the street and ask
them about LP delay, and they'restill kind of mystified.
And part of the reason for thatis it was always thought to be
non-modifiable, but now we knowit is modifiable and probably
(07:29):
safely so.
SPEAKER_00 (07:30):
Getting a little technical, um the the trials
that we're doing now here thatwe are enrolling for involves
something called smallinterfering RNA, which is
another, quote, geneticallybased way of preventing the
assembly of lipoprotein littleA.
And it involves something calledthe RNA-induced silencing
complex, which is part of allthe cells that's actually
(07:51):
trained to look for pieces ofgenetic material that can cause
problems.
It's a sort of an intrinsicmechanism of cells to prevent
viruses from doing damage.
So they're looking for so sortof bad pieces of genetic
material.
And we can train these parts ofthe cells to identify the
strands that are important formaking lipoprotein linol A.
(08:13):
And with this technology, itseems incredibly safe so far.
We're able to reduce levels ofLPA by up to 95%, as mentioned.
So the next step is to seewhether that huge reduction in
LPA will translate into fewerheart attacks and strokes for
people at extremely high risk.
LPA issues are fundamentally a little bit
different than cholesterolissues.
My name is Dr.
Michael Korn, and I'm delightedto moderate another session of
MedEvidence.
And we're very fortunate todayto have a special guest, Dr.
Dennis Leahy from San Diego,who's going to talk about
lipoprotein little A from boththe perspective of a clinical
(00:21):
cardiologist, interventionalcardiologist, and also a patient
that has this problem.
SPEAKER_01 (00:26):
I'm a classic LP little A person in that I had a
very strong family history ofvascular disease.
SPEAKER_00 (00:32):
Probably came mostly from my mother's side of the
family.
This family history concept isreally, really important.
So going back to my cardiologydays, one of the things that
struck me when I first learnedabout LPA is the really, really
strong family history of peoplewith this problem.
So you'll you'll get folks, forexample, that have a father and
mother who had somecomplications in their 20s, 30s,
(00:54):
or 40s.
And this is following eachgeneration down the road.
So uh, and and to that point, uhI I did my training at New York
Hospital, and one of the famousLPA patients at New York
Hospital was Arthur Ash, who hadthis type of family history of
having both mother and fatherhave heart disease at a young
(01:15):
age, and you know, Arthur Ash,as a fit professional athlete,
had his first cardiac issue atage 29.
So it was a very profoundintroduction to me of this
particular problem.
SPEAKER_01 (01:27):
So uh in 2002, you'll probably recall, um LP
little A was it was known.
I mean, it's been known as a asa as a lipid particle for some
time, but uh there's a realstruggle to figure out whether
it's strictly a biomarker orcausative agent for vascular
disease.
And in 2002, things were everybit as murky as they were before
(01:47):
that.
But um I was kind of a typicalLP little A patient and remain
so in that if you look at me andyou looked at 10 other people in
the room, you'd say, who's thelast 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 uhand had other virtually no other
risk factors.
SPEAKER_00 (02:06):
Just for the audience, LPA is measured in
different ways.
In fact, there's kind of adebate of the best way to
measure it.
But the the two major ways ofmeasuring it are either by mass,
and the typical measurementthere is milligrams per
deciliter, or by concentration,and then the typical measurement
would be nanomoles per liter.
(02:27):
And they are related to eachother, but because L uh because
lipoprotein little A is aheterogeneous molecule, more and
more of us think that theconcentration is a better way to
describe it, because eachparticle can actually have a
different mass, and it's hard toknow your risk based on quote
the size of your particles.
(02:48):
So just looking at the overallconcentration of particles is
probably the way most of us aregoing in the lipid field.
SPEAKER_01 (02:55):
So, anyway, um I was uh doing my usual thing, and
then a very uh important momentin my life was uh New Year's
morning on uh 2007.
So this is about four yearsafter I had my my uh negative
calcium scan.
I was surfing.
Uh it was a cold, windy morningfor San Diego and uh kind of an
arduous paddle out.
(03:15):
And I had my first episode ofchest pain when I was paddling
out, and I knew exactly what itwas uh having been uh in this
position with thousands ofpatients over the years.
Kind of backed off and uh andgot into the beach, the the pain
was gone, but I was quitecertain uh I was just I was now
living out my my legacy here asa leahy.
(03:38):
And in indeed, so then I I didget a cardiac workup uh and uh
had some stents placed shortlythereafter.
Uh three months after my stentprocedure, I was surfing, same
beach, same situation, had chestpain again.
SPEAKER_00 (03:53):
Was that your is that is that standard cardiac
rehab in San Diego is surfing?
It is it is for me.
SPEAKER_01 (03:59):
Uh and so sure enough, uh I had rhiztenosis in
in one of the stents.
Um the other one didn't look toobad at that time, and we decided
to stent within the stent with adifferent uh a different
coating.
These were drug-alluding stents.
Never had any issues with bloodpressure, always at ideal
weight, um, no diabetes, uhnever smoker.
(04:22):
It was all it was pretty much LPdelay, and then perhaps not
perfectly ideal LDL, as I saidwith my 2002 readings.
Part of the part of the goodfortune of my story, I guess the
bad fortune is I have thisproblem, but the good fortune is
I've had access to world-classhealthcare, and that's really
gotten me through all thisZionis pharmaceuticals, where
they have developed this um ASOor anti-sense oligonucleotide
(04:45):
treatment for LP Lelay, which isa is a gene-slowing approach to
try to suppress LP Lelayproduction.
Uh they'd had one successfulphase two trial and they were
starting another one.
And it sounded like a greatoption because, unlike other
trials where it's frequently a50-50 chance of getting active
treatment, this was a dosingtrial, so I had a five out of
(05:05):
six chance of actually being onan active drug.
So I was in that in that studyfor one year uh with, as you
know, successful and impressivesuppression of LP delay
production.
Um with a uh I I think I was ona uh once every two-week
injection, subcutaneousinjection.
Uh very simple procedure, whichhas been shown to be quite safe
(05:29):
with uh minimal side effects.
SPEAKER_00 (05:32):
And this is the uh the molecule that we call
pelicarsin now, is that correct?
Right.
Right.
And yeah, antisenseoligonucleotide that actually
prevents the the production ofthe protein that is essential
for the assembly of lipoproteinlay right outside the nucleus of
the of the hepatocytes.
(05:52):
So um that's a fascinatingtechnology and really, really
exciting.
And um so exciting that as Iunderstand it, Novartis uh
bought the product.
SPEAKER_01 (06:02):
Right.
You know, Novartis, of course,is in hopefully towards the end
of a trial, a major, major trialthat will be a really uh, you
know, really a landmark uh kindof pivotal trial of whether
whether these things are goingto result in lower incidence of
cardiovascular events bysuppressing LP little A
production.
The the thing that I haveactually written a couple pieces
(06:23):
on that have been uh kind ofop-eds that have have gotten on
a couple online sites is I feeluh very passionate that everyone
in the world should be testedfor their LP little A level.
I think it's an extremelyimportant part of where we're
going with LP little A.
I don't want to get too far inthe weeds if if this is this is
not something you want topursue, but you only need to be
(06:45):
tested once to be essentially tostratify your risk because the
level doesn't change much uhfrom age five onwards.
Your LP little A level is goingto be your LP little A level.
Well, LP little A has kind ofsuffered uh uh a weird history
in that it really hasn't evergotten the attention it
deserves, even though I thinkparticularly the past decade,
(07:06):
the elegant research that youand other people have been
involved in have reallyclarified its role and given a
direction to how we should treatit.
But that is not translated wellin the clinical world.
You you talk to the averagedoctor on the street and ask
them about LP delay, and they'restill kind of mystified.
And part of the reason for thatis it was always thought to be
non-modifiable, but now we knowit is modifiable and probably
(07:29):
safely so.
SPEAKER_00 (07:30):
Getting a little technical, um the the trials
that we're doing now here thatwe are enrolling for involves
something called smallinterfering RNA, which is
another, quote, geneticallybased way of preventing the
assembly of lipoprotein littleA.
And it involves something calledthe RNA-induced silencing
complex, which is part of allthe cells that's actually
(07:51):
trained to look for pieces ofgenetic material that can cause
problems.
It's a sort of an intrinsicmechanism of cells to prevent
viruses from doing damage.
So they're looking for so sortof bad pieces of genetic
material.
And we can train these parts ofthe cells to identify the
strands that are important formaking lipoprotein linol A.
(08:13):
And with this technology, itseems incredibly safe so far.
We're able to reduce levels ofLPA by up to 95%, as mentioned.
So the next step is to seewhether that huge reduction in
LPA will translate into fewerheart attacks and strokes for
people at extremely high risk.
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