Name: Max Lugavere on Controversial Alzheimer's Drugs and Studies
Uploaded: 2022-09-14T17:33:46.000Z
Description: Watch the stand-up comedy video 'Max Lugavere on Controversial Alzheimer's Drugs and Studies' from PowerfulJRE on Comedy Buff. Published 2022-09-14. Transcript available.

Watch the stand-up comedy video 'Max Lugavere on Controversial Alzheimer's Drugs and Studies' from PowerfulJRE on Comedy Buff. Published 2022-09-14. Transcript available.

- The Joe Rogan Experience.
- Especially in the field of Alzheimer's disease,
there was this huge revelation recently
that the past 16 years of Alzheimer's research
in many ways was built on fraud.
- Yeah, I read that.
That is one of the things that I wanted to talk to you about
because it's so crazy.
Please tell people about this because it's so insane
and it's so hard to believe that this could happen
in modern medicine, especially with something
that affects so many people's Alzheimer's,
but please tell people about this study.
- Yeah, so basically the prevailing hypothesis
as to what causes Alzheimer's disease
over the past century, right,
has been what's called the amyloid hypothesis.
So ever since Alois Alzheimer discovered
or named Alzheimer's disease in 1906
and looked into the brain of the cadaver
and saw these plaques aggregating around neurons, right,
in the extracellular space around neurons,
the plaques have come to be sort of the force,
the focus of Alzheimer's research, really.
And the idea was that these plaques were the causative force
in the condition.
Much like the plaque on your teeth, right?
You see these plaques in the brain of a person
with Alzheimer's disease.
And so that's really been the target of drug therapy.
And the idea was that until we can find a drug
that would reduce the plaque burden, reduce the plaque,
get rid of the plaque in the brains of a senior person, right,
somebody who's at risk for developing Alzheimer's disease,
that it's a disease that you can't prevent.
There's nothing to do to treat.
But the problem was that they can never actually tie the plaque
to cognitive decline, right?
Like the clinically meaningful symptom,
the symptomology of Alzheimer's disease,
that it messes up your cognition,
that it makes you, you know,
that it makes you forget your loved ones,
ultimately forget who you are,
ultimately forgetting how to eat, right,
and nourish yourself.
They could never tie those symptoms to the plaque, right?
Until a paper published in the journal Nature in 2006.
So what happened was this researcher named Sylvain Lesney
at the University of Minnesota
basically was looking into these,
the brains of mice who are bred to overexpress
what's called amyloid precursor protein,
which is the precursor to amyloid beta,
which is the protein that makes up
sort of the skeleton of these plaques
that we see aggregate, right?
So what he did was he isolated a subtype
that he called A-beta star 56
and injected it into a young and healthy mouse
or rat, mouse.
And he saw that that mouse's cognition rapidly declined.
So that was the missing link, right,
that he found a subtype of this amyloid beta protein
that serves as the backbone of these plaques,
which could never be pinned to the cognitive decline itself, right,
the memory loss itself.
But he claimed that he found it
and when injected into the brain,
into the body of a healthy mouse,
he saw a rapid decline in terms of their cognition, right?
So that was the missing link.
And so at that point,
faith in the so-called amyloid hypothesis was starting to wane
because they couldn't find effective drugs.
Alzheimer's drug trials have a 99.6% fail rate.
So worse than for cancer or worse than for any other disease state, really.
And the drugs that are currently FDA-approved on the market,
they're biochemical Band-Aids.
They're minimally effective.
I mean, they modulate various neurotransmitters.
But, you know, I've heard it described like, you know,
expecting to remove amyloid from the brain of a person with Alzheimer's disease
and to see their cognition come back
is sort of like thinking that if you remove all the headstones from a grave,
you know, the people will come back to life, right?
Like there's widespread neuronal dysfunction and death
in the brain of somebody with Alzheimer's disease.
And in tandem with that,
scanning technology has allowed us to look into the brains of healthy controls.
And what we see is that there's amyloid plaque
in the brains of healthy controls as well.
So there's no correlation between amyloid burden in the brain
and one's cognitive abilities.
But nonetheless, when this paper came out in 2006,
it renewed fervor in terms of this hypothesis
because he found the subtype of amyloid
that could be injected into a young and healthy mouse
that would then seriously impair their cognition, right?
And so that renewed interest in this hypothesis.
And it's what ultimately led to the fact that just a couple years ago,
two years ago,
there was a highly controversial drug that was approved by the FDA
called aducanumab or aduhelm.
And this is a drug
that effectively reduced plaque burden in the brain.
For the first time,
they found a drug that could actually reduce plaque burden in the brain.
But it didn't lead to any improvement in cognitive symptoms.
Nonetheless,
it was given the green light against tons of opposition that the FDA received.
They put together a panel of 11 people,
neuroscientists, neurologists, right?
Eight of them told the FDA not to approve this drug.
And what was the reason for that?
The reason for that was that the drug
didn't move the needle on any clinically meaningful symptom.
Were there significant side effects for the drug?
There were.
So 35% of the people in the trial had significant brain swelling
and half of them had bleeding associated with that brain swelling
because these are antibodies.
So aducanumab is an antibody that basically targets,
causes your own immune system to target the amyloid plaques, right?
And so what that's doing is causing an inflammatory response in the brain,
right?
So 35% of the patients in that, in the, in the phase two trials, I believe,
had horrible side effects and no clinically meaningful, uh, effect on, um, on
their cognition.
But nonetheless, because it effectively did reduce the amyloid plaque burden,
there was this intense pressure, right?
To, uh, to get it greenlit because that's like the amyloid hypothesis right
there, right?
Uh-huh.
So huge problem.
One of the big, uh, vocal sort of skeptics about this drug, aducanumab,
is a guy, a Vanderbilt researcher named Matthew Schrag.
And so Matthew Schrag was, like, very vocal, vocally against the approval of
this drug,
which, again, doesn't do anything, right?
Like, horrible risk of side effects, no clinically meaningful effect on, on, on
the,
on the symptoms that we want to improve, right, um, for a patient with
Alzheimer's disease.
And, um, and so he was vocally critical of that.
And then he also was working on some other, some other drug.
And he, uh, so, uh, what was revealed basically in the science paper that came
out was that
he was, um, dabbling in, uh, on a website called PubPeer, which is, um, a site
where you can go,
it's known for post-publication peer review.
So before paper gets, uh, accepted for publication, it undergoes this peer
review process, right?
And so he found that there were a lot of sort of red flags that were being
brought up on this message board,
essentially, about this nature paper, this, like, seminal nature paper that was
published,
that found to, it was, like, the missing link, right, between, like, the amyloid
hypothesis
and, like, the clinically meaningful, meaningful, um, symptoms, meaning memory
loss.
And he did a bit of, like, image sleuthing, which is not generally part of the
peer review process, right?
And he looked at these, um, the way data is illustrated in this, in this paper,
as it is in, in research,
generally, it's called a Western blot, which is, like, a visual representation
of, of data,
the presence of proteins and so forth.
And he found that they were all, for the most part, fabricated.
In fact, this A beta star 56 wasn't found by any other team, hasn't been found
by any other team.
It, it, it basically came to light that it was essentially fake.
The whole thing was faked.
What was the motivation for this person to fake all this?
Because the thing, I mean, I think that we, we like to believe that science is
this good faith endeavor
towards human flourishing, right?
But in the industry of science, there are flawed humans, just like there are in
every other industry, right?
And scientists in general, I see this all the time in nutrition, online, on
social media, right?
Social media is a great, like, sort of, they say that sunlight is the best
disinfectant.
Like, social media is a great way to kind of see how this plays out.
Right.
Because scientists are notoriously territorial, obstinate, they, you know,
their, their reputations,
egotistical, yeah, their reputations are everything, right?
Yeah.
And, um, I mean, it's just like, I see it, I see it every day.
I see humans.
Yeah, exactly.
Yeah.
So, yeah, so there's bad apples, right?
Like, I think a lot of people in science, um, like, I'm, I'm, I live and
breathe nutrition.
I'm, it's the thing that I'm most passionate about, like, in life, right?
Like, fitness, nutrition, sleep, disease prevention.
My mom is what galvanized that, that passion for me, right?
And what, what my mom, my mom went through and my desire to prevent it from
happening to others that I care about.
And ultimately people, you know, from all walks of life.
But a lot, you know, a lot of people go into science, go into medicine because
it's just, it's a career path.
Right.
Right.
It's a career path for somebody wanting validation.
It comes with prestige.
It comes with money.
It comes with all the things that, that, like, make sense that a person would
want, right?
But then ego gets in the way and it, and it becomes really problematic.
I mean, you see it in nutrition all the time.
You see it in nutrition, like, all the freaking time.
So this person that fabricated this study and fabricated all this data, what
consequences are there for that person?
I mean, I think that the, the Department of Justice is, is going to be looking
into it, but, but, um.
They're going to be looking into it.
I mean, this is.
If they're not already.
Yeah.
Yeah.
If they're not already.
But I personally, so one of the worst things about this, right, is it's not
just like the lost time and all the money that went to continue looking down
this sort of path of the amyloid hypothesis, right?
Looking in the wrong place, really.
Because amyloid is there, but it's sort of like what you see in cholesterol, in
like atherosclerosis, right?
Like cholesterol.
It's like everybody, like, has pointed at cholesterol as being the bad guy
because cholesterol is clearly there in atherosclerotic plaques, right?
But what's causing it to be there?
That's the question that these researchers should have been asking all along.
And some have, right?
Like there, there have been other, like my mentor, as I mentioned, you know, at
Cornell, who I've been lucky to lucky enough to work with over the years on
certain projects, you know, knew that there was another way.
It's this glucose hypometabolism, right?
It's like, but there's no money in that.
There's no money in saying, like, make your, keep yourself as insulin sensitive
as possible.
You know, reduce your exposure to environmental pollutants.
Don't hit your head too hard.
You know, all these different modifiable risk factors.
It's not as, it's not, it's not druggable the way that this like amyloid beta
protein is, is druggable.
And so I think the worst thing about it is that anybody who would advance an
alternate viewpoint over the past couple of decades would be ridiculed and silenced
by the quote amyloid mafia.
And I was the, I, I, this happened to me when I first started doing my
documentary, um, little empty boxes, which when I first started doing it, uh,
it had a different name.
I called it, it was called breadhead.
And I could talk about why I named it that, but that was always a sort of a
working title, uh, for the project.
But somebody at one of these foundations, right?
Like, um, there's all these like big, like Alzheimer's foundations.
Uh, I'm lucky to be working on this project with one who really believes in me
and the project, the Alzheimer's foundation of America, but there are these
other nonprofits that really what they are is just like a front for, you know,
perpetuating the status quo and keeping the sort of the funding pipeline open
for drug discovery.
And so when I first got started doing, working on this, on my film, I did a
Kickstarter campaign for it.
And one of these non pro quote unquote nonprofits, right.
Deeply invested in the amyloid hypothesis came out and wrote an, uh, an op ed
in the wall street journal, disparaging me and my project and any other
alternate sort of viewpoint and talking glowingly about that aducanumab drug,
which at the time had yet to be approved.
Right. And it was so like painful to me at the time because I was like working
on this project out of the love and passion that I had for my mom and my desire
to get the science out to catalyze, you know, interest in this science.
It takes 17 years on average for what's discovered in science to be put into
day to day clinical practice.
So I was like, that's, that's time we don't have to lose when the brains of our
loved ones are at stake.
And so, yeah, I was like directly sort of in the crosshairs at the time for
this, like this amyloid mafia.
I was like directly affected by it because this medication is profitable.
Yeah.
Because the medication is profitable and that the whole avenue was thought to,
you know, if you could find a drug that would reduce amyloid burden in the
brain, I mean, that makes, that's going to make shareholders really happy.
And this drug, is it still being prescribed?
Yeah.
It's, uh, it's, uh, it's approved.
It's approved.
And so there's no real way of telling how many people have died from this drug
because most of the people that are taking this drug already are experiencing
this neurodegenerative disease and you could easily chalk it off to that being
the cause of death.
Yeah.
I mean, I, I can't speak to like, you know, people's experiences on it
currently, but I do know that, um, that the trials were, you know, I mean, if I
had a loved one based on what I was doing,
what I know about this drug and those trials, I, my, my loved one currently
would not be on that drug.
They would be perhaps experimenting with, uh, you know, and this is a very
difficult sort of road to go down.
I guess it's easier to say if I had dementia, right?
If I myself had dementia, I would be experimenting with a ketogenic diet on
myself and other ketogenic therapies because ketogenic diets, what they do.
So, so as I mentioned in the Alzheimer's brain, the ability to generate energy
from glucose is reduced by about 50%, 45, 50%.
It's ability to generate energy from ketone bodies is unperturbed.
So the idea is that a ketogenic diet can essentially keep the lights on in the
Alzheimer's brain.
It's not a cure, but, um, but there has been, uh, research, um, on patients
with Alzheimer's disease, mild to moderate Alzheimer's disease, that ketogenic,
a ketogenic diet intervention can actually improve functional capacity in those
patients, which is everything, right?

Max Lugavere on Controversial Alzheimer's Drugs and Studies

- The Joe Rogan Experience.
- Especially in the field of Alzheimer's disease,
there was this huge revelation recently
that the past 16 years of Alzheimer's research
in many ways was built on fraud.
- Yeah, I read that.
That is one of the things that I wanted to talk to you about
because it's so crazy.
Please tell people about this because it's so insane
and it's so hard to believe that this could happen
in modern medicine, especially with something
that affects so many people's Alzheimer's,
but please tell people about this study.
- Yeah, so basically the prevailing hypothesis
as to what causes Alzheimer's disease
over the past century, right,
has been what's called the amyloid hypothesis.
So ever since Alois Alzheimer discovered
or named Alzheimer's disease in 1906
and looked into the brain of the cadaver
and saw these plaques aggregating around neurons, right,
in the extracellular space around neurons,
the plaques have come to be sort of the force,
the focus of Alzheimer's research, really.
And the idea was that these plaques were the causative force
in the condition.
Much like the plaque on your teeth, right?
You see these plaques in the brain of a person
with Alzheimer's disease.
And so that's really been the target of drug therapy.
And the idea was that until we can find a drug
that would reduce the plaque burden, reduce the plaque,
get rid of the plaque in the brains of a senior person, right,
somebody who's at risk for developing Alzheimer's disease,
that it's a disease that you can't prevent.
There's nothing to do to treat.
But the problem was that they can never actually tie the plaque
to cognitive decline, right?
Like the clinically meaningful symptom,
the symptomology of Alzheimer's disease,
that it messes up your cognition,
that it makes you, you know,
that it makes you forget your loved ones,
ultimately forget who you are,
ultimately forgetting how to eat, right,
and nourish yourself.
They could never tie those symptoms to the plaque, right?
Until a paper published in the journal Nature in 2006.
So what happened was this researcher named Sylvain Lesney
at the University of Minnesota
basically was looking into these,
the brains of mice who are bred to overexpress
what's called amyloid precursor protein,
which is the precursor to amyloid beta,
which is the protein that makes up
sort of the skeleton of these plaques
that we see aggregate, right?
So what he did was he isolated a subtype
that he called A-beta star 56
and injected it into a young and healthy mouse
or rat, mouse.
And he saw that that mouse's cognition rapidly declined.
So that was the missing link, right,
that he found a subtype of this amyloid beta protein
that serves as the backbone of these plaques,
which could never be pinned to the cognitive decline itself, right,
the memory loss itself.
But he claimed that he found it
and when injected into the brain,
into the body of a healthy mouse,
he saw a rapid decline in terms of their cognition, right?
So that was the missing link.
And so at that point,
faith in the so-called amyloid hypothesis was starting to wane
because they couldn't find effective drugs.
Alzheimer's drug trials have a 99.6% fail rate.
So worse than for cancer or worse than for any other disease state, really.
And the drugs that are currently FDA-approved on the market,
they're biochemical Band-Aids.
They're minimally effective.
I mean, they modulate various neurotransmitters.
But, you know, I've heard it described like, you know,
expecting to remove amyloid from the brain of a person with Alzheimer's disease
and to see their cognition come back
is sort of like thinking that if you remove all the headstones from a grave,
you know, the people will come back to life, right?
Like there's widespread neuronal dysfunction and death
in the brain of somebody with Alzheimer's disease.
And in tandem with that,
scanning technology has allowed us to look into the brains of healthy controls.
And what we see is that there's amyloid plaque
in the brains of healthy controls as well.
So there's no correlation between amyloid burden in the brain
and one's cognitive abilities.
But nonetheless, when this paper came out in 2006,
it renewed fervor in terms of this hypothesis
because he found the subtype of amyloid
that could be injected into a young and healthy mouse
that would then seriously impair their cognition, right?
And so that renewed interest in this hypothesis.
And it's what ultimately led to the fact that just a couple years ago,
two years ago,
there was a highly controversial drug that was approved by the FDA
called aducanumab or aduhelm.
And this is a drug
that effectively reduced plaque burden in the brain.
For the first time,
they found a drug that could actually reduce plaque burden in the brain.
But it didn't lead to any improvement in cognitive symptoms.
Nonetheless,
it was given the green light against tons of opposition that the FDA received.
They put together a panel of 11 people,
neuroscientists, neurologists, right?
Eight of them told the FDA not to approve this drug.
And what was the reason for that?
The reason for that was that the drug
didn't move the needle on any clinically meaningful symptom.
Were there significant side effects for the drug?
There were.
So 35% of the people in the trial had significant brain swelling
and half of them had bleeding associated with that brain swelling
because these are antibodies.
So aducanumab is an antibody that basically targets,
causes your own immune system to target the amyloid plaques, right?
And so what that's doing is causing an inflammatory response in the brain,
right?
So 35% of the patients in that, in the, in the phase two trials, I believe,
had horrible side effects and no clinically meaningful, uh, effect on, um, on
their cognition.
But nonetheless, because it effectively did reduce the amyloid plaque burden,
there was this intense pressure, right?
To, uh, to get it greenlit because that's like the amyloid hypothesis right
there, right?
Uh-huh.
So huge problem.
One of the big, uh, vocal sort of skeptics about this drug, aducanumab,
is a guy, a Vanderbilt researcher named Matthew Schrag.
And so Matthew Schrag was, like, very vocal, vocally against the approval of
this drug,
which, again, doesn't do anything, right?
Like, horrible risk of side effects, no clinically meaningful effect on, on, on
the,
on the symptoms that we want to improve, right, um, for a patient with
Alzheimer's disease.
And, um, and so he was vocally critical of that.
And then he also was working on some other, some other drug.
And he, uh, so, uh, what was revealed basically in the science paper that came
out was that
he was, um, dabbling in, uh, on a website called PubPeer, which is, um, a site
where you can go,
it's known for post-publication peer review.
So before paper gets, uh, accepted for publication, it undergoes this peer
review process, right?
And so he found that there were a lot of sort of red flags that were being
brought up on this message board,
essentially, about this nature paper, this, like, seminal nature paper that was
published,
that found to, it was, like, the missing link, right, between, like, the amyloid
hypothesis
and, like, the clinically meaningful, meaningful, um, symptoms, meaning memory
loss.
And he did a bit of, like, image sleuthing, which is not generally part of the
peer review process, right?
And he looked at these, um, the way data is illustrated in this, in this paper,
as it is in, in research,
generally, it's called a Western blot, which is, like, a visual representation
of, of data,
the presence of proteins and so forth.
And he found that they were all, for the most part, fabricated.
In fact, this A beta star 56 wasn't found by any other team, hasn't been found
by any other team.
It, it, it basically came to light that it was essentially fake.
The whole thing was faked.
What was the motivation for this person to fake all this?
Because the thing, I mean, I think that we, we like to believe that science is
this good faith endeavor
towards human flourishing, right?
But in the industry of science, there are flawed humans, just like there are in
every other industry, right?
And scientists in general, I see this all the time in nutrition, online, on
social media, right?
Social media is a great, like, sort of, they say that sunlight is the best
disinfectant.
Like, social media is a great way to kind of see how this plays out.
Right.
Because scientists are notoriously territorial, obstinate, they, you know,
their, their reputations,
egotistical, yeah, their reputations are everything, right?
Yeah.
And, um, I mean, it's just like, I see it, I see it every day.
I see humans.
Yeah, exactly.
Yeah.
So, yeah, so there's bad apples, right?
Like, I think a lot of people in science, um, like, I'm, I'm, I live and
breathe nutrition.
I'm, it's the thing that I'm most passionate about, like, in life, right?
Like, fitness, nutrition, sleep, disease prevention.
My mom is what galvanized that, that passion for me, right?
And what, what my mom, my mom went through and my desire to prevent it from
happening to others that I care about.
And ultimately people, you know, from all walks of life.
But a lot, you know, a lot of people go into science, go into medicine because
it's just, it's a career path.
Right.
Right.
It's a career path for somebody wanting validation.
It comes with prestige.
It comes with money.
It comes with all the things that, that, like, make sense that a person would
want, right?
But then ego gets in the way and it, and it becomes really problematic.
I mean, you see it in nutrition all the time.
You see it in nutrition, like, all the freaking time.
So this person that fabricated this study and fabricated all this data, what
consequences are there for that person?
I mean, I think that the, the Department of Justice is, is going to be looking
into it, but, but, um.
They're going to be looking into it.
I mean, this is.
If they're not already.
Yeah.
Yeah.
If they're not already.
But I personally, so one of the worst things about this, right, is it's not
just like the lost time and all the money that went to continue looking down
this sort of path of the amyloid hypothesis, right?
Looking in the wrong place, really.
Because amyloid is there, but it's sort of like what you see in cholesterol, in
like atherosclerosis, right?
Like cholesterol.
It's like everybody, like, has pointed at cholesterol as being the bad guy
because cholesterol is clearly there in atherosclerotic plaques, right?
But what's causing it to be there?
That's the question that these researchers should have been asking all along.
And some have, right?
Like there, there have been other, like my mentor, as I mentioned, you know, at
Cornell, who I've been lucky to lucky enough to work with over the years on
certain projects, you know, knew that there was another way.
It's this glucose hypometabolism, right?
It's like, but there's no money in that.
There's no money in saying, like, make your, keep yourself as insulin sensitive
as possible.
You know, reduce your exposure to environmental pollutants.
Don't hit your head too hard.
You know, all these different modifiable risk factors.
It's not as, it's not, it's not druggable the way that this like amyloid beta
protein is, is druggable.
And so I think the worst thing about it is that anybody who would advance an
alternate viewpoint over the past couple of decades would be ridiculed and silenced
by the quote amyloid mafia.
And I was the, I, I, this happened to me when I first started doing my
documentary, um, little empty boxes, which when I first started doing it, uh,
it had a different name.
I called it, it was called breadhead.
And I could talk about why I named it that, but that was always a sort of a
working title, uh, for the project.
But somebody at one of these foundations, right?
Like, um, there's all these like big, like Alzheimer's foundations.
Uh, I'm lucky to be working on this project with one who really believes