July 30, 2024 • 39 mins
Gary Gravina, a skilled carpenter and Marine, was rushed to the ER in 2016 due to severe flu-like symptoms which morphed into a brutal battle with a mysterious disease. Discover how Gary's dire condition would lead him to Dr. David Fajgenbaum and Dr. Grant Mitchell, who had become experts on his rare disease. See how their collaboration not only saved Gary’s life but also significantly impacted the field of medicine.
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If you’re looking for information on Castleman disease or if would like to find out more about the work of Grant, David, and the Every Cure team, visit EveryCure.org.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:01):
Previously unsymptomatic. David Fegenbaum, a college quarterback deeply impacted by
his mother's fight with brain cancer, was a prime example
of peak health and motivation.
Speaker 2 (00:15):
The moment that I saw her dealing with her cancer,
I just said, this is what I have to spend
the rest of my life doing. And by this, it's
taking care of people with horrible diseases, and it's searching
for treatments so that people don't suffer.
Speaker 1 (00:31):
But during med school, everything quickly came crashing down when
Castleman disease took him from treating patients to the brink
of death in a matter of days.
Speaker 2 (00:41):
I was so sick that my doctors encouraged my family
to say goodbye to me.
Speaker 3 (00:47):
I'll never forget the moment when a priest came in
and read him his last rites. In this moment of sorrow,
I remember I couldn't really keep it together, I couldn't
hide help. Horrifying it was to see him in that state.
Speaker 1 (01:01):
After exhausting all the treatments available for Castleman, David's body
was ravaged by chemo and he was out of viable options.
That's when he decided to take matters into his own hands.
Speaker 2 (01:14):
I had to take some action, and it had to
be a pretty crazy step, and that is to start
testing one of these drugs that I was studying in
the lab on myself. All the drugs I was studying
the lab were all ft approved for something else, they
just weren't used for Castlemen.
Speaker 1 (01:28):
After repurposing a medicine originally designed for kidney transplant patients
to send his disease into long term remission, David was
determined to prevent others from that similar dead end. His
theories around expanding the approved uses for certain medicines would
quickly be put to the test. Seeing Gary Gravina fight
for his life against Castleman, just like David had a
(01:51):
few short years before.
Speaker 2 (01:54):
Yes, his heart is technically beating. Yes he's technically breathing
because of what we're doing medically, but he's not going
to come back from this. And I just remember being
so devastated to hear that, and then at the same
time remember still running down the hall to the lab
and still running the experiments because like who knows, there was.
Speaker 4 (02:15):
At least one night in both of my flares where
it was just that close. I was in a coma.
You know, everything in me was tanking, and I can
just remember crying tears of frustration.
Speaker 1 (02:33):
How terrifying would it be to fight an unknown enemy,
one you didn't recognize and didn't see coming. What if
that enemy was coming from within a disease that even
doctors couldn't identify. Nearly half of all Americans suffer from
some chronic illness, and many struggle for an accurate diagnosis.
(02:57):
These are their stories, Lauren Bribe Pacheco, and this is symptomatic.
(03:18):
Gary Gravina built a life working with his hands, first
as a marine and then as a carpenter for over
twenty seven years. He felt fulfilled when he could craft something,
even if it was just a song on his guitar.
Before Gary would face a fight for his life, he
and his wife Stacy had been hit with their first
seemingly insurmountable hurdle.
Speaker 4 (03:39):
Let's see about nine months after we all moved in together,
my steps on Jacob presented with a seizure and had
a diagnostic journey that the end result was that he
had brain cancer, and so we were heavily engaged in
fighting that for just over a year. They had given
(04:00):
him six months to maybe a year to live as
the original prognosis, which being Jake. He beat that by
a week.
Speaker 1 (04:09):
Wow.
Speaker 4 (04:10):
It was huge. It was traumatic, and there was all
this medical acquaintance that we wish we never had. And
when the doctor said there was nothing more they could do,
we were preparing hospice and we had the hospital bed
being sent here.
Speaker 1 (04:26):
Oh Gary, I'm so sorry.
Speaker 4 (04:28):
Yeah, thank you.
Speaker 1 (04:30):
So you had already been through the ringer before you
even realized you had symptoms.
Speaker 4 (04:35):
Yeah, something like that happened, and you think, wow, that
was the most awful thing, and you kind of in
the back of your head, you're thinking, that must have
been our big, awful thing that we have to overcome.
Speaker 1 (04:45):
But it was not long until Gary started noticing his
body change. Heavy fatigue made getting through the day more
of a chore than usual. Looking back, now, what are
some of the earliest symptoms.
Speaker 4 (05:00):
You can pinpoint the morning when I felt ill, like
I felt like I had a flu, but I could
not push through it. I could not get up and
go to work. And I mean for the previous eighteen years,
I think I had taken off two and a half
days of sick time. I just did not miss work
if I felt sick during the day, I pushed through
(05:21):
the end of the day. I got some rest that night,
and then the next morning I came in and started
to feel better. But this wasn't happening. And I took
one day off and I did not feel any better,
and so I say, it felt like a flu, that
achy feeling, that drained feeling, and the swimminess in my head.
My wife started to notice that my stomach was getting larger,
(05:44):
and I wasn't really eating because I felt so ill,
and so for me to be putting on weight was weird.
So Stacy said, you know, we have to get you
to the doctor. The next thing I remember was being
at the doctor and him listening to my lungs and saying,
you need to get to the host hospital.
Speaker 1 (06:01):
Wow. And at what point did they realize they were
dealing with something far more serious than the flow.
Speaker 4 (06:08):
That whole first day at the emergency room, I'm thinking, well,
this is going to be something really simple and they're
going to take care of it. And then when they
started talking about admitting me, I'm like, come on, this
is this is not something like that. I don't need
to be in the hospital. This is ridiculous. I just
this sense of this, this is all just a big mistake.
(06:29):
By the end of that week, I was in a
medically induced coma, and I don't think I really squared
myself with that until I woke up, you know, three
and a half weeks later. What was going on going
into the hospital, it was this sense was frustration, like this,
we just need to find the thing that this is.
And this should be a simple answer. I shouldn't. I
(06:51):
shouldn't be here.
Speaker 1 (06:56):
Though Gary didn't know it. As he endured the challenges
of his undiagnosed Castleman disease, David was hard at work
in a lab not far away. Through the creation of
the Castleman Disease Collaborative Network or CDCN, David was honoring
his mission to repurpose drugs that could treat Castleman disease
and other immuno deficiency conditions. There are only three thousand
(07:21):
FDA approved drugs, and ninety five percent of rare diseases
have no medical approved treatment in terms of medication.
Speaker 2 (07:32):
That's right, there's so much here. I mean, all I've
been able to think about for these last ten years
is how many more drugs are sitting out there. They
could be life saving for other people and what we've learned.
The more I've done it, the more I've just been
blown away by the fact that of those three thousand drugs,
the vast majority of them are generic. Over eighty percent
(07:53):
of them are generic, which means that they are very
inexpensive and they're not profitable any longer because once it
drug becomes generic, then multiple manufacturers can make that drug
price plummets. And so what that means is that our
medical system doesn't study over eighty percent of our drugs
that are at the CBS to find new uses for
them because there is no incentive within our system. And
(08:15):
it's like, wait a minute, of the drugs, the three
thousand that can help us, eighty percent of them are
not being studied. That's crazy.
Speaker 1 (08:26):
It wasn't always smooth sailing for the CDCN. David shared
his dream with Grant, his best friend from medical school,
but they were up against lots of skepticism from the
medical community to make it happen. Tell me just a
little bit about thinking outside the box in terms of
(08:46):
wanting to evaluate medicines that already had FDA approval but
for off label impact.
Speaker 3 (08:56):
Yeah, and maybe before I do that, I'll tell you
one more story about our sort of naive optimism. When
we first realized that we were going to try to
be they, we called everyone we knew to currently be they,
which was all the researchers in the world that might
know anything about this disease. There were only twenty of
(09:19):
them or so. They were in France and Japan at
the NIH and we invited them all to a conference
that they might have been interested in attending anyway, and said,
if you're already going to be there, you know, please
come to this side room with David and I to
discuss Castleman disease research. And I'll never forget sitting there
at the head of the table with David said this
(09:41):
is David. I'm grant, you know, and we're here to
cure Castleman disease, and just seeing these researchers who had
been at this for years around the table kind of
chuckle and say, okay, kids, you know, good luck. You know,
we'll try and be helpful. It was just one of
those moments where we were young and naive enough to have
(10:01):
the audacity to think that we could do anything.
Speaker 1 (10:04):
This passionate naivete needed to change from an inspiring concept
to a reality quickly if it was going to save
Gary from arreparable damage. After the first flare up, Gary
was now going in and out of medically induced comas,
clinging to life. He was eventually diagnosed with Castleman disease,
the same disease that plagued David years earlier. However, the
(10:28):
diagnosis didn't guarantee a clear path to effective treatment. When
you first woke up and you felt and saw the
physical transformations of your body coming out of that coma,
how surreal was that for you? That must have been
(10:50):
honestly like living an episode of the Twilight Zone.
Speaker 4 (10:55):
Yeah, coming out of a coma, at least for me,
was nothing like the show it in TV and movie
where you open your eyes and you look up and
you see your loved one and you remember the last
thing that was going on. It's a kind of a
slow drift back toward reality.
Speaker 5 (11:11):
And then also, you know, as the head of the family,
I can't imagine how heavily it weighed on you that
this is happening again and you're not there to physically
fight it.
Speaker 4 (11:27):
Yeah, that was huge because with Jacob, I was by
Stacy's side as a caregiver, helping her take care of him,
and then in this situation, suddenly Stacy was back in
the role of caregiver, and my condition was plummeting. And
part of the reason I was so frustrated and wanted
(11:48):
to figure out the simple thing that this had to
be was that I didn't want to be the reason
that Stacy went.
Speaker 1 (11:54):
To that again, grappling with guilt. On top of the
physical fight for his life. Even additional symptoms pile up,
and so I.
Speaker 4 (12:03):
Woke up with purple hands and they felt gravelly, they
felt sandy. They were numb, but also uncomfortable. You know,
it was not the biggest pain that I had, but
it was very uncomfortable because I've always used my hands
for everything I do, and so to have them not
there was really it was freaky. Once I did wake up,
(12:26):
I had to be fed by hand because my arms
were so weak and my stomach had grown so large,
like I couldn't put my hands together. I didn't have
enough strength to reach up that high. So Stacy was
spoon feeding me my food when I came out of
the coma. When people talk about having an advocate, man,
I had the best doctors and nurses in the world,
(12:46):
And I mean I'm very grateful for that, but I
would be dead. I would be dead without Stacy if
she hadn't been there to do what she did.
Speaker 1 (13:00):
Local doctors had exhausted all of the known treatments for
Castleman disease and had decided to transfer Gary to the
hospital of the University of Pennsylvania for more help.
Speaker 4 (13:11):
David Figenbaum had released a study on Castleman disease. Actually
the day I went into the hospital, he published this
in esh newsletter for Heematology, because I think the journal
is called Blood it is. And someone at the second
hospital had seen that article. One of the people said, well,
this guy, he has the disease and he's fighting it.
(13:33):
And so I ended up done at penn and I'm.
Speaker 2 (13:36):
Told, hey, there's a patient with your subtype of Castleman's.
You know, this very rare subtype of Castlemans that's here
in the ICU. Can you go up and see the patient?
And at this stage, I'm working in the hospital, I'm
running the center that does a lot of research, but
I'm like fiercely avoiding the ICU, like I don't want
to walk anywhere near the ic I got some bad
memories FM when I was in the ICU.
Speaker 4 (13:56):
And I was nervous. It was almost I was nervous
like you would be for a job application, like like
I hope he lets me in, you know what I mean.
It's so weird. And of course you just hear, you know,
doctor researcher, and you hear the name doctor Fagenbaum, and
it's a beautiful name. It just it kind of sounds
like old doctor. So I'm picturing an old, gray haired
(14:18):
guy with glasses and probably broken from the disease, but
still moving on. And then this young guy comes in
looking full of life, and like all the fight in
him and the spirit and the keenness of his intellect
and how compassionate he was was just like, wow, okay,
I'll take a pass on lymphoma. I'll take what that
(14:40):
guy has. It's the craziest thing I remember, like it
was yesterday. I see a patient in the bad who
is so sick. All of his organs are obviously failing,
and he looks just like me when I was at
my sickest, Like he's got the fluid. When you lose
the muscles in your face, you sort of look like,
(15:00):
you know, you have these dense next to your eyes.
Speaker 2 (15:03):
Everything. It was like I'm looking at I'm like, oh
my gosh, he he just looks so much like me.
And then b I look and I see his wife Stacy,
and I like see in her eyes this deep concern,
this care. You can just see right away that like,
you know, this is her everything right now in the
hospital bed and she's losing him, and it's like you
(15:24):
just feel it when you see her. And I look
at this window and I'm like, I recognize this view.
Speaker 1 (15:34):
You've said that when David first visited you that you
immediately clutched at the hope that you could get there,
that you could get where he is. Did that tap
into your like marine determination spirit?
Speaker 4 (15:50):
Yeah, that, and in particular that he was leading a
research effort and said that I could contribute to it,
that I could not only fight my way out of
the bed, but help him the whole disease was huge.
To turn from this helpless two hundred and sixty pound
bag of fluid into somebody who was fighting was a
(16:11):
huge turning point for me up until that point. It
was something that I was looking for, and that was
part of my frustration, like why can't we take care
of this? Why can't we hit this back, and so
that was the turning point where he said, you know,
will you contribute samples to the research and that was
no brainer I was. I was like, hell, yes.
Speaker 2 (16:32):
I remember telling him that you know, we're going to
beat this, and I really believe it because i'd been
in his bed, although a minute or two later I
learned that literally had been in his bed because when
I walked out, one of the nurses came over and
gave me a hug, and I actually didn't know who
she was or you know, what was going on, and
she said, I was your nurse when you were here
a few years ago, which I didn't realize. Was again,
(16:54):
when you're a nice you oftentimes you know you're just
out of it, and so I didn't realize that. And
she said, and this was your hospital room, and I
was like, oh my gosh. That's why I recognized that
view out the window because that's the window I'd been
looking at for weeks and weeks and weeks, and I
just dreamed. I was like, one day I could get
out of here.
Speaker 1 (17:12):
I get the hairs on my arms, stand up on
that It's amazing. In the same exact shoes and room
as David once was. The challenge was now to rethink
Gary's treatment. Under the care of David and the CDCN,
who were busily working behind the scenes on repurposed treatment
(17:32):
options for rare diseases, there was a renewed sense of hope.
Speaker 2 (17:37):
Well, first you got a Castleman's drug that we thought
would work, and that drug seemed to work a little bit,
and then he relapsed, and then we ended up giving
him a bunch of chemotherapy that sort of seemed to
work and get him out of this thing. But the
question became, how do we keep it from coming back.
We were getting blood samples on Gary basically every day,
and as soon as we get the blood sample, we'd
(17:59):
run down to the lab. We'd run something called flow sytometry,
and we were getting results back and looking at those
results and then saying, you know, is there a different
drug we should be using based on what we're seeing
in the lab. And it was like this race against time.
Speaker 1 (18:12):
It was clear to everyone that Gary's time was running out.
His body was too weak to push through continued chemotherapy.
David and the CDCN needed to produce results immediately if
they were going to save Gary's life.
Speaker 2 (18:25):
I get so excited every time we save a life
and we find a drug that can help someone, and
that's it's just incredible. But even more incredible, or at
least even greater of a feeling than how thankful we
are when it works, is just how devastated we are
when these drugs don't work. And it's both of those
emotions that just drive us to keep working. You get
a carrot and a stick, and it's just like you're
(18:47):
just constantly chasing, and you get constantly motivated by both
the people who are here because of our work and
also the people who aren't here despite our work.
Speaker 1 (18:57):
Gary, was there a time time that you felt like
it was pointless to keep fighting? Were you in that
much exhaustion and pain at any point to think I
can't do this? And what was it that pulled you
out of that? So?
Speaker 4 (19:15):
I would visualize them as scenarios, But what I kept
feeling was myself approaching some sort of a boundary or
a doorway or that sort of thing. And it wasn't
like a blessed realm where your loved ones come and
say now is not your time? Or you know, there
were no singing or anything like that. I would always
see my wife and my kids, and I would turn
(19:35):
away from that and turn turn toward them with my will.
The first flare was I am not going anywhere near there.
I want to find the way toward what I knew.
I wanted to find my way toward awareness. I was
so frustrated that we know what this is. Why am
I still here? Why am I stuck in the state.
None of us liked the lows. I wish I could
(19:58):
give all these lows back. But the lows in some
ways can really create this sort of like potential energy
or like this like slingshot effect, and then it's that
horrible moment that results in action, and that action results
in something that we celebrate.
Speaker 1 (20:21):
We'll be right back with Symptomatic a Medical Mystery Podcast.
Now back to Symptomatic a Medical Mystery Podcast. Gary Gravina,
a former carpenter and marine, went from his usual routine
to being placed in a medically induced coma within a week.
(20:44):
Having supported his wife through the loss of his stepson,
Gary was determined to prevent her from experiencing that pain again.
But after the treatment for his Castleman disease had failed,
Gary's last hope was the research on alternative treatments from
doctor David Fagenbaum. Initially, though I know that they had
(21:07):
tried a medicine that had worked on other Castleman's patients
that didn't work on you. Was there in those initial
attempts to find what for you could be the silver bullet?
Was it devastating or was it more just like bring
on the next No?
Speaker 4 (21:26):
And when I think about David having five flares, there
was a difference in my energy. I was on celtuxamab
to get out of the first flare, and I thought
that was going to do it. And I think after
my third treatment, my blood all looked like it was
trending in the right direction. And then like a week later,
I was going into my second flare and it was
(21:47):
just not working anymore. It had quit, and I thought,
oh no, not again, Like can this just be some
other thing that's going on a side effect? But it
had that same feeling, that same I cannot lift myself
to push through this. The day before at physical therapy,
I was pushing and pushing and getting better and better
(22:09):
results every day, and there were stuff I just couldn't
do that day, and the physical therapist said, you know,
make sure you reach out to your doctor and let
them know that you've had this little turning point.
Speaker 1 (22:20):
Despite some signs of relief and a brief return to routine,
Castleman continually returned, sending Gary back to the ICU and
David back to the drawing board.
Speaker 4 (22:31):
Even during my second player being comatose again. That fueled
the anger that we know what this is? Why am
I stuck in the state again? And you're in the
ice your room, and you know all the things are
connected to you, and you're just kind of you feel
apart from everything, and you start to wonder why am
I being singled out? Like am I being punished?
Speaker 3 (22:52):
What did I do?
Speaker 4 (22:53):
I must have done something to deserve this, And I
can just remember crying tears of frustration.
Speaker 5 (23:01):
David.
Speaker 1 (23:03):
It has to be kind of like solving a puzzle
and playing chess at the same time.
Speaker 2 (23:08):
Yes, that's exactly right. And I think that for me.
You know, before I got into this world, when I
heard a doctor say we've tried everything, there's nothing more
that we can do. I sort of assumed that meant that,
like there were no more chess pieces on the chess
board and there were no more puzzle pieces. But I
think what I've subsequently learned is that when a doctor
(23:30):
says we've tried everything, many times I think they are
right and that there isn't actually something that could help
that patient. But many times I also believe, and I've
seen and witnessed that actually there is something that we
can do. There is that chess piece that's on the board,
but we the medical community, just haven't unlocked the potential
(23:50):
of it.
Speaker 1 (23:52):
Grant breaks down why rare diseases are often referred to
as orphans.
Speaker 3 (23:57):
An orphan disease is very much what it sounds like.
It's a disease that very few people get, defined by
less than two hundred thousand people having it, and it
actually represents the majority of the diseases that are out there,
depending on how you count diseases. But let's say if
there's twelve thousand, the vast majority, let's say almost nine
(24:17):
thousand of those are rare, and most of those don't
have an approved treatment, not a single approved treatment. Ninety
five percent of rare diseasees don't have a single afday
approved treatment.
Speaker 1 (24:27):
Wow, because there's not the money in it, because the
numbers aren't driving it.
Speaker 3 (24:33):
Yeah, and you know, the pharmaceutical industry. It's a business,
and they are shared holders, and there's fiduciary obligations to
those shareholders to make money and return their capital. So
I don't blame them for not focusing on diseases that
don't make money. That's how the free market works. But
that means that there's a lot of diseases that ultimately
(24:56):
get neglected and there's no incentive to focus on them,
and so that really bothered us.
Speaker 1 (25:03):
Gary David talks about a point where he was told
by one of the nurses that you weren't gonna make it.
Speaker 4 (25:11):
Yeah, and I think there was at least one night
in both of my flares where it was just that close.
But I was in a coma and he was there
with Stacy during the second flare, and I was just,
you know, everything in me was tanking.
Speaker 2 (25:26):
He was on a ventilator, he was receiving what are
called pressers, which is basically, when your heart's failing, you
give drugs to keep the heart beating as best as
it can, even though it's like basically dying. Without the pressers,
you die. But just trying to say, you know, we're
we're still looking for drugs for you, Gary, like I'm
gonna take your sample to the lab. We're going to
keep fighting for you. And as I walked out of
(25:48):
his room, I remember his nurse pulling me aside and saying, David,
this is it. You know, I'm an ice, you nurse,
this is what I do. I'm seeing the changes in
his hands and his feet that occur when they're is
no coming back, Like, yes, his heart is technically beating. Yes,
he's technically breathing because of what we're doing medically, but
he's not going to come back from this. And I
(26:10):
just remember being so so devastated to hear that, and
then at the same time remember still running down the
hall to the lab and still running the experiments because
like who knows.
Speaker 4 (26:22):
And he was telling Stacy, there is hope, don't give
up hope. And as he was leaving, this ICU nurse
who had actually been there when he was there, said,
you should not have told her that you're giving her
false hope. He's not going to make it through the night.
And my understanding is she went in and told Stacy
he's that bad. You need to be ready for that.
Speaker 2 (26:44):
And we still ran the fless atometry and a sample,
and we still thought about work for the next drug
be but I.
Speaker 4 (26:48):
Mean it to them, meant.
Speaker 1 (26:53):
Gary not only survived the night, but made it through
the entire flare up. David and the CDCN found it
treatment regimen that put his Castleman disease into remission, one
that was originally developed and approved to treat lymphoma. As
the weeks passed and turned into months, they realized this
repurposed to medicine had given Gary a second chance at life. So, David,
(27:17):
if you can think of what if you look back,
is probably the highest happiest moment in terms of Gary.
Speaker 2 (27:24):
There are a few. I think seeing him get into
a wheelchair and get rolled out of his hospital room
was just amazing. You know, shortly before that we didn't
know if he was going to make it, and then
now I get to watch him, you know, get wheeled
down the hall.
Speaker 4 (27:39):
If I don't feel a flare coming on, I have today,
and today is beautiful. It's good. It makes me enjoy
moments more, and it makes me more ready to accept
other setbacks because a different sense of scale and proportion
when problems arise, I see what can continue. I see
a way to fight through those things a little better
(28:01):
knowing that, you know, if I wake up tomorrow, that
could be the last thing I remember for a long
time before I start that fight all over again.
Speaker 1 (28:09):
Grant and David maintain their collaboration through the early days
of their divergent career paths, continually coming back to the
idea of scaling the cdcn's research. Impacted by Gary's experience
and the rise of AI data aggregation, they saw new
potential for revolutionizing their approach to repurposing medicines.
Speaker 2 (28:31):
And so Grant and I spent a lot of time
thinking about could we start an initiative, an effort to
try to unlock more uses for fdapproved drugs. In about
two years ago is when we launched this nonprofit called
every Year, and we are on a mission to unlock.
Speaker 3 (28:46):
The life saving potential of every FDA approved medication to
treat every disease that it possibly can. There's nothing more
motivating that seeing a patient that is now able to
be with their family and live their life to their
fullest because of the science that you did. It's an
amazing thing that you get to participate in. And so
(29:07):
that's always the sort of the guiding light, the north star.
Speaker 1 (29:13):
So David how did Gary's case play a big part
of the evolution of every cure?
Speaker 2 (29:20):
You know, my book's called Chasing My Cure, because of
course this all started out well, even before Chasing My Cure,
it was obviously witnessing my mom's battle, but this all
really started with Chasing My Cure. And I've said before
and I really believe it, we should have called it
Chasing our Cure, because, as you know, and as you've
heard us discussed, there were a lot of people part
of us. It was actually not me, it was a
lot of us, But it started out that way. But
(29:42):
then for every patient like Gary, for every patient like
Kyla who's getting ready to go off to college because
we discovered a drug to save her life just before
she would have passed, and patients like Joseph who right
now is recovering after we found a drug to save
his life just a few months ago. Each one of
those patients has just led us to say, we are
(30:03):
so happy we did this for them, But how many
more they're out there?
Speaker 3 (30:06):
And what began to dawn on us throughout the years,
because my career went off into the world of machine
learning and AI, was that the way to unlock this
problem that we have been able to start as a
business is potentially to use artificial intelligence and structured as
a nonprofit, and that was really what unlocked our next
(30:30):
sort of journey, which was become every cure grant.
Speaker 1 (30:34):
It's brilliant, it really is. A lot of people are
frightened by AI, but I can't think of a more
wonderful way to utilize it.
Speaker 3 (30:44):
This technology could be utilized in maybe a different context
that maybe instead of focusing on one drug and one
disease at a time for a company, maybe we could
widen the lens. Maybe we could look across all diseases
and all drugs and find the interconnectivity between them to
(31:05):
figure out which drugs should work for which diseases.
Speaker 1 (31:08):
With all the conversations and fear around AI and its
evolution upending certain industries, it's heartening to see a powerful
and potentially transformative application to save people's lives and offer
different treatment options for rare diseases.
Speaker 2 (31:25):
Over the last few years, even just the last two years,
there has been so many advances so that whereas what
we used to do in my lab, where we would
study Castlin disease for example, or related diseases, you know,
we spend years working on a proteomic study or sequencing study,
for example, years to come up with an insight. We're
really proud of the progress we've made. But now utilizing
(31:48):
artificial intelligence, we can actually apply AI to the world's
biomedical knowledge.
Speaker 3 (31:53):
And we would talk all the time about what is
the potential here, what is the potential to scale what's
happening in lab by doing it in the data and
then doing it beyond just one drug and one disease
at a time, And we would check in on this
every few years. Twenty sixteen, it wasn't really possible to
think as big as we were thinking. The data just
(32:16):
wasn't there, And it really wasn't until the last few
years that it started to dawn on us that maybe
something truly was possible here. So ultimately, what we do
is we compile every kind of data that exists in
the world that might be able to link one biomedical
(32:36):
concept to another. So does a drug hit a target,
where is that target on this protein, what gene generates
that protein, what pathway does that protein sit in, what
cell type, what organ system.
Speaker 2 (32:51):
Of course, the predictions are not going to be perfect,
and we're not going to say, oh, just because it's
number one on our list, it's going to work for everyone.
We still need to do clinical trials to validate it,
but the ability to focus in on all the possibilities
to the ones that look most promising is just something
that's never been possible before in human history.
Speaker 1 (33:09):
Grant, what are you most proud of in terms of
every cure?
Speaker 3 (33:14):
I think I'm most proud of the fact that we
have not let this go. And then I'm so proud
of the people that come and join our team. These
are some of the smartest people in the world that
could have higher paying jobs, that could be in Silicon
Valley doing other things, and they are compelled by this mission.
(33:37):
They're compelled by the ability to relieve suffering and save lives,
and they're compelled by the opportunity to create an engine
that should outlast us and will save lives in perpetuity,
whether we're working at every cure or not. In the future,
we want to create something that lasts in something that
(33:58):
has major impact.
Speaker 2 (34:00):
Over fifteen drug where we've identified in or advanced a
repurpose drug for a disease they weren't intended for. And
I'm so proud of that.
Speaker 1 (34:08):
Through the work at the CDCN and every cure over
the past ten years, David and Grant have tirelessly worked
to prevent others from enduring the suffering of orphan diseases.
David and Gary were both on the brink of death,
told there was nothing left to do, just to find
out that a medicine that already existed could be the cure.
(34:30):
Despite having every reason to give up, they persevered, Gary,
what do you want people to take away from your
experience and what got you through it?
Speaker 4 (34:41):
Well, that's a toughye. So through the CDCN, I try
and act as an ambassador to other people who are
facing Castle and disease and just let them note that
they're not alone. It was right after my last round
of chemo and the second FLARE that I attended the
first Patient Loved One summit. I was in a room
full of sixty people who had Castle of disease or
(35:04):
who had a loved one who had Castle and disease.
And so when I talked about that sense of having
felt singled out and being punished, that was the polar opposite.
That was a huge turning point to be around other
people who they're describing things, and I'm like, yeah, I
get that. So that was a big thing for me
to really learn to enjoy connecting with people. And you
(35:25):
just have that sense of other people being with you.
You fight better when you have somebody by.
Speaker 1 (35:31):
Your side, especially someone like doctor David Fagenbaum. I have
to tell you it is such a comfort to me
to know that people like you exist. And I am
deeply indebted to your mother, thank you, and to your father,
your sisters, to Caitlin, because anybody who has gotten you
(35:55):
through what you've gone through to make it possible for
me to be sitting and talking to you today honestly
in their debt and the world is too. I don't
say that lightly. What do you want people to take
away from your story, from your personal challenges?
Speaker 2 (36:12):
I think the things that immediately come to mind are
that no matter how tough things get, no matter how
low the odds are, no matter how difficult things are,
I think just realizing that there may be a path
out of this. At the same time, I think it's
also important emphasize that the path out isn't necessarily going
(36:35):
to be delivered on your door, and that for me,
the reason I'm alive is not because I got really
lucky multiple times. It's because I had the right circumstances
around me, the amazing family, the amazing support, and I
started taking action. And that doesn't mean that anyone who's
dealing with illness or death needs to start experimenting on
(36:58):
their own blood samples or starting a grief organization. But
it does mean that you need to take action in
ways that makes sense for you. And so that might
be getting involved with the disease organization for the disease
that you have. It might be driving in your car
to the world's expert because, like you know, your local
doctor isn't doing what you need. I do think it
(37:18):
takes action.
Speaker 1 (37:21):
If you'd like to find out more about the work
Grant and David and the rest of the team at
Every Cure Doing, visit Everycure dot org. They emphasize the
importance of raising awareness and donations as the best way
to support their ongoing efforts.
Speaker 4 (37:36):
My name is Gary Gravina, I'm David Fagenbaum, and I
fought Casselman disease for nine months.
Speaker 2 (37:43):
And after nearly dying five times in three years from
a deadly disease called Castleman.
Speaker 4 (37:48):
Disease, David Fagenbaum and the CDCN came up with a
regimen that has held me in remission. I've now been
alive for over ten years, for almost eight years now.
Speaker 2 (37:58):
Thanks to a drug that I discovered that I had
been sitting on my pharmacy shelf all along, and now
I'm on a mission to try to find as many
more uses of existing drugs as possible to save as
many lives as possible.
Speaker 1 (38:12):
Next week on Symptomatic, we dive into the modern landscape
of prostate cancer and care. We'll explore emerging therapies, new research,
and some of the biggest hurdles faced by both patients
and healthcare professionals when trying to fight this deadly disease.
We're also excited to announce that Symptomatic will return for
a full season later this year. Thank you for trusting
(38:36):
us to share your stories. If you've experienced a mysterious
diagnostic journey or have a story of interest you want
to share, reach out to us at Symptomatic at iHeartMedia
dot com and keep an eye on your feed Until then,
Stay well. Symptomatic Medical Mystery Podcast is a production of
(38:56):
Ruby Studio from iHeartMedia. Our show is hosted by me
Lauren breg Pacheco. Executive producers are Matt Romano and myself.
Our EP of post production is James Foster. Our producers
are Sierra Kaiser and John Irwin. And this episode was
researched by Diana Davis
Previously unsymptomatic. David Fegenbaum, a college quarterback deeply impacted by
his mother's fight with brain cancer, was a prime example
of peak health and motivation.
Speaker 2 (00:15):
The moment that I saw her dealing with her cancer,
I just said, this is what I have to spend
the rest of my life doing. And by this, it's
taking care of people with horrible diseases, and it's searching
for treatments so that people don't suffer.
Speaker 1 (00:31):
But during med school, everything quickly came crashing down when
Castleman disease took him from treating patients to the brink
of death in a matter of days.
Speaker 2 (00:41):
I was so sick that my doctors encouraged my family
to say goodbye to me.
Speaker 3 (00:47):
I'll never forget the moment when a priest came in
and read him his last rites. In this moment of sorrow,
I remember I couldn't really keep it together, I couldn't
hide help. Horrifying it was to see him in that state.
Speaker 1 (01:01):
After exhausting all the treatments available for Castleman, David's body
was ravaged by chemo and he was out of viable options.
That's when he decided to take matters into his own hands.
Speaker 2 (01:14):
I had to take some action, and it had to
be a pretty crazy step, and that is to start
testing one of these drugs that I was studying in
the lab on myself. All the drugs I was studying
the lab were all ft approved for something else, they
just weren't used for Castlemen.
Speaker 1 (01:28):
After repurposing a medicine originally designed for kidney transplant patients
to send his disease into long term remission, David was
determined to prevent others from that similar dead end. His
theories around expanding the approved uses for certain medicines would
quickly be put to the test. Seeing Gary Gravina fight
for his life against Castleman, just like David had a
(01:51):
few short years before.
Speaker 2 (01:54):
Yes, his heart is technically beating. Yes he's technically breathing
because of what we're doing medically, but he's not going
to come back from this. And I just remember being
so devastated to hear that, and then at the same
time remember still running down the hall to the lab
and still running the experiments because like who knows, there was.
Speaker 4 (02:15):
At least one night in both of my flares where
it was just that close. I was in a coma.
You know, everything in me was tanking, and I can
just remember crying tears of frustration.
Speaker 1 (02:33):
How terrifying would it be to fight an unknown enemy,
one you didn't recognize and didn't see coming. What if
that enemy was coming from within a disease that even
doctors couldn't identify. Nearly half of all Americans suffer from
some chronic illness, and many struggle for an accurate diagnosis.
(02:57):
These are their stories, Lauren Bribe Pacheco, and this is symptomatic.
(03:18):
Gary Gravina built a life working with his hands, first
as a marine and then as a carpenter for over
twenty seven years. He felt fulfilled when he could craft something,
even if it was just a song on his guitar.
Before Gary would face a fight for his life, he
and his wife Stacy had been hit with their first
seemingly insurmountable hurdle.
Speaker 4 (03:39):
Let's see about nine months after we all moved in together,
my steps on Jacob presented with a seizure and had
a diagnostic journey that the end result was that he
had brain cancer, and so we were heavily engaged in
fighting that for just over a year. They had given
(04:00):
him six months to maybe a year to live as
the original prognosis, which being Jake. He beat that by
a week.
Speaker 1 (04:09):
Wow.
Speaker 4 (04:10):
It was huge. It was traumatic, and there was all
this medical acquaintance that we wish we never had. And
when the doctor said there was nothing more they could do,
we were preparing hospice and we had the hospital bed
being sent here.
Speaker 1 (04:26):
Oh Gary, I'm so sorry.
Speaker 4 (04:28):
Yeah, thank you.
Speaker 1 (04:30):
So you had already been through the ringer before you
even realized you had symptoms.
Speaker 4 (04:35):
Yeah, something like that happened, and you think, wow, that
was the most awful thing, and you kind of in
the back of your head, you're thinking, that must have
been our big, awful thing that we have to overcome.
Speaker 1 (04:45):
But it was not long until Gary started noticing his
body change. Heavy fatigue made getting through the day more
of a chore than usual. Looking back, now, what are
some of the earliest symptoms.
Speaker 4 (05:00):
You can pinpoint the morning when I felt ill, like
I felt like I had a flu, but I could
not push through it. I could not get up and
go to work. And I mean for the previous eighteen years,
I think I had taken off two and a half
days of sick time. I just did not miss work
if I felt sick during the day, I pushed through
(05:21):
the end of the day. I got some rest that night,
and then the next morning I came in and started
to feel better. But this wasn't happening. And I took
one day off and I did not feel any better,
and so I say, it felt like a flu, that
achy feeling, that drained feeling, and the swimminess in my head.
My wife started to notice that my stomach was getting larger,
(05:44):
and I wasn't really eating because I felt so ill,
and so for me to be putting on weight was weird.
So Stacy said, you know, we have to get you
to the doctor. The next thing I remember was being
at the doctor and him listening to my lungs and saying,
you need to get to the host hospital.
Speaker 1 (06:01):
Wow. And at what point did they realize they were
dealing with something far more serious than the flow.
Speaker 4 (06:08):
That whole first day at the emergency room, I'm thinking, well,
this is going to be something really simple and they're
going to take care of it. And then when they
started talking about admitting me, I'm like, come on, this
is this is not something like that. I don't need
to be in the hospital. This is ridiculous. I just
this sense of this, this is all just a big mistake.
(06:29):
By the end of that week, I was in a
medically induced coma, and I don't think I really squared
myself with that until I woke up, you know, three
and a half weeks later. What was going on going
into the hospital, it was this sense was frustration, like this,
we just need to find the thing that this is.
And this should be a simple answer. I shouldn't. I
(06:51):
shouldn't be here.
Speaker 1 (06:56):
Though Gary didn't know it. As he endured the challenges
of his undiagnosed Castleman disease, David was hard at work
in a lab not far away. Through the creation of
the Castleman Disease Collaborative Network or CDCN, David was honoring
his mission to repurpose drugs that could treat Castleman disease
and other immuno deficiency conditions. There are only three thousand
(07:21):
FDA approved drugs, and ninety five percent of rare diseases
have no medical approved treatment in terms of medication.
Speaker 2 (07:32):
That's right, there's so much here. I mean, all I've
been able to think about for these last ten years
is how many more drugs are sitting out there. They
could be life saving for other people and what we've learned.
The more I've done it, the more I've just been
blown away by the fact that of those three thousand drugs,
the vast majority of them are generic. Over eighty percent
(07:53):
of them are generic, which means that they are very
inexpensive and they're not profitable any longer because once it
drug becomes generic, then multiple manufacturers can make that drug
price plummets. And so what that means is that our
medical system doesn't study over eighty percent of our drugs
that are at the CBS to find new uses for
them because there is no incentive within our system. And
(08:15):
it's like, wait a minute, of the drugs, the three
thousand that can help us, eighty percent of them are
not being studied. That's crazy.
Speaker 1 (08:26):
It wasn't always smooth sailing for the CDCN. David shared
his dream with Grant, his best friend from medical school,
but they were up against lots of skepticism from the
medical community to make it happen. Tell me just a
little bit about thinking outside the box in terms of
(08:46):
wanting to evaluate medicines that already had FDA approval but
for off label impact.
Speaker 3 (08:56):
Yeah, and maybe before I do that, I'll tell you
one more story about our sort of naive optimism. When
we first realized that we were going to try to
be they, we called everyone we knew to currently be they,
which was all the researchers in the world that might
know anything about this disease. There were only twenty of
(09:19):
them or so. They were in France and Japan at
the NIH and we invited them all to a conference
that they might have been interested in attending anyway, and said,
if you're already going to be there, you know, please
come to this side room with David and I to
discuss Castleman disease research. And I'll never forget sitting there
at the head of the table with David said this
(09:41):
is David. I'm grant, you know, and we're here to
cure Castleman disease, and just seeing these researchers who had
been at this for years around the table kind of
chuckle and say, okay, kids, you know, good luck. You know,
we'll try and be helpful. It was just one of
those moments where we were young and naive enough to have
(10:01):
the audacity to think that we could do anything.
Speaker 1 (10:04):
This passionate naivete needed to change from an inspiring concept
to a reality quickly if it was going to save
Gary from arreparable damage. After the first flare up, Gary
was now going in and out of medically induced comas,
clinging to life. He was eventually diagnosed with Castleman disease,
the same disease that plagued David years earlier. However, the
(10:28):
diagnosis didn't guarantee a clear path to effective treatment. When
you first woke up and you felt and saw the
physical transformations of your body coming out of that coma,
how surreal was that for you? That must have been
(10:50):
honestly like living an episode of the Twilight Zone.
Speaker 4 (10:55):
Yeah, coming out of a coma, at least for me,
was nothing like the show it in TV and movie
where you open your eyes and you look up and
you see your loved one and you remember the last
thing that was going on. It's a kind of a
slow drift back toward reality.
Speaker 5 (11:11):
And then also, you know, as the head of the family,
I can't imagine how heavily it weighed on you that
this is happening again and you're not there to physically
fight it.
Speaker 4 (11:27):
Yeah, that was huge because with Jacob, I was by
Stacy's side as a caregiver, helping her take care of him,
and then in this situation, suddenly Stacy was back in
the role of caregiver, and my condition was plummeting. And
part of the reason I was so frustrated and wanted
(11:48):
to figure out the simple thing that this had to
be was that I didn't want to be the reason
that Stacy went.
Speaker 1 (11:54):
To that again, grappling with guilt. On top of the
physical fight for his life. Even additional symptoms pile up,
and so I.
Speaker 4 (12:03):
Woke up with purple hands and they felt gravelly, they
felt sandy. They were numb, but also uncomfortable. You know,
it was not the biggest pain that I had, but
it was very uncomfortable because I've always used my hands
for everything I do, and so to have them not
there was really it was freaky. Once I did wake up,
(12:26):
I had to be fed by hand because my arms
were so weak and my stomach had grown so large,
like I couldn't put my hands together. I didn't have
enough strength to reach up that high. So Stacy was
spoon feeding me my food when I came out of
the coma. When people talk about having an advocate, man,
I had the best doctors and nurses in the world,
(12:46):
And I mean I'm very grateful for that, but I
would be dead. I would be dead without Stacy if
she hadn't been there to do what she did.
Speaker 1 (13:00):
Local doctors had exhausted all of the known treatments for
Castleman disease and had decided to transfer Gary to the
hospital of the University of Pennsylvania for more help.
Speaker 4 (13:11):
David Figenbaum had released a study on Castleman disease. Actually
the day I went into the hospital, he published this
in esh newsletter for Heematology, because I think the journal
is called Blood it is. And someone at the second
hospital had seen that article. One of the people said, well,
this guy, he has the disease and he's fighting it.
(13:33):
And so I ended up done at penn and I'm.
Speaker 2 (13:36):
Told, hey, there's a patient with your subtype of Castleman's.
You know, this very rare subtype of Castlemans that's here
in the ICU. Can you go up and see the patient?
And at this stage, I'm working in the hospital, I'm
running the center that does a lot of research, but
I'm like fiercely avoiding the ICU, like I don't want
to walk anywhere near the ic I got some bad
memories FM when I was in the ICU.
Speaker 4 (13:56):
And I was nervous. It was almost I was nervous
like you would be for a job application, like like
I hope he lets me in, you know what I mean.
It's so weird. And of course you just hear, you know,
doctor researcher, and you hear the name doctor Fagenbaum, and
it's a beautiful name. It just it kind of sounds
like old doctor. So I'm picturing an old, gray haired
(14:18):
guy with glasses and probably broken from the disease, but
still moving on. And then this young guy comes in
looking full of life, and like all the fight in
him and the spirit and the keenness of his intellect
and how compassionate he was was just like, wow, okay,
I'll take a pass on lymphoma. I'll take what that
(14:40):
guy has. It's the craziest thing I remember, like it
was yesterday. I see a patient in the bad who
is so sick. All of his organs are obviously failing,
and he looks just like me when I was at
my sickest, Like he's got the fluid. When you lose
the muscles in your face, you sort of look like,
(15:00):
you know, you have these dense next to your eyes.
Speaker 2 (15:03):
Everything. It was like I'm looking at I'm like, oh
my gosh, he he just looks so much like me.
And then b I look and I see his wife Stacy,
and I like see in her eyes this deep concern,
this care. You can just see right away that like,
you know, this is her everything right now in the
hospital bed and she's losing him, and it's like you
(15:24):
just feel it when you see her. And I look
at this window and I'm like, I recognize this view.
Speaker 1 (15:34):
You've said that when David first visited you that you
immediately clutched at the hope that you could get there,
that you could get where he is. Did that tap
into your like marine determination spirit?
Speaker 4 (15:50):
Yeah, that, and in particular that he was leading a
research effort and said that I could contribute to it,
that I could not only fight my way out of
the bed, but help him the whole disease was huge.
To turn from this helpless two hundred and sixty pound
bag of fluid into somebody who was fighting was a
(16:11):
huge turning point for me up until that point. It
was something that I was looking for, and that was
part of my frustration, like why can't we take care
of this? Why can't we hit this back, and so
that was the turning point where he said, you know,
will you contribute samples to the research and that was
no brainer I was. I was like, hell, yes.
Speaker 2 (16:32):
I remember telling him that you know, we're going to
beat this, and I really believe it because i'd been
in his bed, although a minute or two later I
learned that literally had been in his bed because when
I walked out, one of the nurses came over and
gave me a hug, and I actually didn't know who
she was or you know, what was going on, and
she said, I was your nurse when you were here
a few years ago, which I didn't realize. Was again,
(16:54):
when you're a nice you oftentimes you know you're just
out of it, and so I didn't realize that. And
she said, and this was your hospital room, and I
was like, oh my gosh. That's why I recognized that
view out the window because that's the window I'd been
looking at for weeks and weeks and weeks, and I
just dreamed. I was like, one day I could get
out of here.
Speaker 1 (17:12):
I get the hairs on my arms, stand up on
that It's amazing. In the same exact shoes and room
as David once was. The challenge was now to rethink
Gary's treatment. Under the care of David and the CDCN,
who were busily working behind the scenes on repurposed treatment
(17:32):
options for rare diseases, there was a renewed sense of hope.
Speaker 2 (17:37):
Well, first you got a Castleman's drug that we thought
would work, and that drug seemed to work a little bit,
and then he relapsed, and then we ended up giving
him a bunch of chemotherapy that sort of seemed to
work and get him out of this thing. But the
question became, how do we keep it from coming back.
We were getting blood samples on Gary basically every day,
and as soon as we get the blood sample, we'd
(17:59):
run down to the lab. We'd run something called flow sytometry,
and we were getting results back and looking at those
results and then saying, you know, is there a different
drug we should be using based on what we're seeing
in the lab. And it was like this race against time.
Speaker 1 (18:12):
It was clear to everyone that Gary's time was running out.
His body was too weak to push through continued chemotherapy.
David and the CDCN needed to produce results immediately if
they were going to save Gary's life.
Speaker 2 (18:25):
I get so excited every time we save a life
and we find a drug that can help someone, and
that's it's just incredible. But even more incredible, or at
least even greater of a feeling than how thankful we
are when it works, is just how devastated we are
when these drugs don't work. And it's both of those
emotions that just drive us to keep working. You get
a carrot and a stick, and it's just like you're
(18:47):
just constantly chasing, and you get constantly motivated by both
the people who are here because of our work and
also the people who aren't here despite our work.
Speaker 1 (18:57):
Gary, was there a time time that you felt like
it was pointless to keep fighting? Were you in that
much exhaustion and pain at any point to think I
can't do this? And what was it that pulled you
out of that? So?
Speaker 4 (19:15):
I would visualize them as scenarios, But what I kept
feeling was myself approaching some sort of a boundary or
a doorway or that sort of thing. And it wasn't
like a blessed realm where your loved ones come and
say now is not your time? Or you know, there
were no singing or anything like that. I would always
see my wife and my kids, and I would turn
(19:35):
away from that and turn turn toward them with my will.
The first flare was I am not going anywhere near there.
I want to find the way toward what I knew.
I wanted to find my way toward awareness. I was
so frustrated that we know what this is. Why am
I still here? Why am I stuck in the state.
None of us liked the lows. I wish I could
(19:58):
give all these lows back. But the lows in some
ways can really create this sort of like potential energy
or like this like slingshot effect, and then it's that
horrible moment that results in action, and that action results
in something that we celebrate.
Speaker 1 (20:21):
We'll be right back with Symptomatic a Medical Mystery Podcast.
Now back to Symptomatic a Medical Mystery Podcast. Gary Gravina,
a former carpenter and marine, went from his usual routine
to being placed in a medically induced coma within a week.
(20:44):
Having supported his wife through the loss of his stepson,
Gary was determined to prevent her from experiencing that pain again.
But after the treatment for his Castleman disease had failed,
Gary's last hope was the research on alternative treatments from
doctor David Fagenbaum. Initially, though I know that they had
(21:07):
tried a medicine that had worked on other Castleman's patients
that didn't work on you. Was there in those initial
attempts to find what for you could be the silver bullet?
Was it devastating or was it more just like bring
on the next No?
Speaker 4 (21:26):
And when I think about David having five flares, there
was a difference in my energy. I was on celtuxamab
to get out of the first flare, and I thought
that was going to do it. And I think after
my third treatment, my blood all looked like it was
trending in the right direction. And then like a week later,
I was going into my second flare and it was
(21:47):
just not working anymore. It had quit, and I thought,
oh no, not again, Like can this just be some
other thing that's going on a side effect? But it
had that same feeling, that same I cannot lift myself
to push through this. The day before at physical therapy,
I was pushing and pushing and getting better and better
(22:09):
results every day, and there were stuff I just couldn't
do that day, and the physical therapist said, you know,
make sure you reach out to your doctor and let
them know that you've had this little turning point.
Speaker 1 (22:20):
Despite some signs of relief and a brief return to routine,
Castleman continually returned, sending Gary back to the ICU and
David back to the drawing board.
Speaker 4 (22:31):
Even during my second player being comatose again. That fueled
the anger that we know what this is? Why am
I stuck in the state again? And you're in the
ice your room, and you know all the things are
connected to you, and you're just kind of you feel
apart from everything, and you start to wonder why am
I being singled out? Like am I being punished?
Speaker 3 (22:52):
What did I do?
Speaker 4 (22:53):
I must have done something to deserve this, And I
can just remember crying tears of frustration.
Speaker 5 (23:01):
David.
Speaker 1 (23:03):
It has to be kind of like solving a puzzle
and playing chess at the same time.
Speaker 2 (23:08):
Yes, that's exactly right. And I think that for me.
You know, before I got into this world, when I
heard a doctor say we've tried everything, there's nothing more
that we can do. I sort of assumed that meant that,
like there were no more chess pieces on the chess
board and there were no more puzzle pieces. But I
think what I've subsequently learned is that when a doctor
(23:30):
says we've tried everything, many times I think they are
right and that there isn't actually something that could help
that patient. But many times I also believe, and I've
seen and witnessed that actually there is something that we
can do. There is that chess piece that's on the board,
but we the medical community, just haven't unlocked the potential
(23:50):
of it.
Speaker 1 (23:52):
Grant breaks down why rare diseases are often referred to
as orphans.
Speaker 3 (23:57):
An orphan disease is very much what it sounds like.
It's a disease that very few people get, defined by
less than two hundred thousand people having it, and it
actually represents the majority of the diseases that are out there,
depending on how you count diseases. But let's say if
there's twelve thousand, the vast majority, let's say almost nine
(24:17):
thousand of those are rare, and most of those don't
have an approved treatment, not a single approved treatment. Ninety
five percent of rare diseasees don't have a single afday
approved treatment.
Speaker 1 (24:27):
Wow, because there's not the money in it, because the
numbers aren't driving it.
Speaker 3 (24:33):
Yeah, and you know, the pharmaceutical industry. It's a business,
and they are shared holders, and there's fiduciary obligations to
those shareholders to make money and return their capital. So
I don't blame them for not focusing on diseases that
don't make money. That's how the free market works. But
that means that there's a lot of diseases that ultimately
(24:56):
get neglected and there's no incentive to focus on them,
and so that really bothered us.
Speaker 1 (25:03):
Gary David talks about a point where he was told
by one of the nurses that you weren't gonna make it.
Speaker 4 (25:11):
Yeah, and I think there was at least one night
in both of my flares where it was just that close.
But I was in a coma and he was there
with Stacy during the second flare, and I was just,
you know, everything in me was tanking.
Speaker 2 (25:26):
He was on a ventilator, he was receiving what are
called pressers, which is basically, when your heart's failing, you
give drugs to keep the heart beating as best as
it can, even though it's like basically dying. Without the pressers,
you die. But just trying to say, you know, we're
we're still looking for drugs for you, Gary, like I'm
gonna take your sample to the lab. We're going to
keep fighting for you. And as I walked out of
(25:48):
his room, I remember his nurse pulling me aside and saying, David,
this is it. You know, I'm an ice, you nurse,
this is what I do. I'm seeing the changes in
his hands and his feet that occur when they're is
no coming back, Like, yes, his heart is technically beating. Yes,
he's technically breathing because of what we're doing medically, but
he's not going to come back from this. And I
(26:10):
just remember being so so devastated to hear that, and
then at the same time remember still running down the
hall to the lab and still running the experiments because
like who knows.
Speaker 4 (26:22):
And he was telling Stacy, there is hope, don't give
up hope. And as he was leaving, this ICU nurse
who had actually been there when he was there, said,
you should not have told her that you're giving her
false hope. He's not going to make it through the night.
And my understanding is she went in and told Stacy
he's that bad. You need to be ready for that.
Speaker 2 (26:44):
And we still ran the fless atometry and a sample,
and we still thought about work for the next drug
be but I.
Speaker 4 (26:48):
Mean it to them, meant.
Speaker 1 (26:53):
Gary not only survived the night, but made it through
the entire flare up. David and the CDCN found it
treatment regimen that put his Castleman disease into remission, one
that was originally developed and approved to treat lymphoma. As
the weeks passed and turned into months, they realized this
repurposed to medicine had given Gary a second chance at life. So, David,
(27:17):
if you can think of what if you look back,
is probably the highest happiest moment in terms of Gary.
Speaker 2 (27:24):
There are a few. I think seeing him get into
a wheelchair and get rolled out of his hospital room
was just amazing. You know, shortly before that we didn't
know if he was going to make it, and then
now I get to watch him, you know, get wheeled
down the hall.
Speaker 4 (27:39):
If I don't feel a flare coming on, I have today,
and today is beautiful. It's good. It makes me enjoy
moments more, and it makes me more ready to accept
other setbacks because a different sense of scale and proportion
when problems arise, I see what can continue. I see
a way to fight through those things a little better
(28:01):
knowing that, you know, if I wake up tomorrow, that
could be the last thing I remember for a long
time before I start that fight all over again.
Speaker 1 (28:09):
Grant and David maintain their collaboration through the early days
of their divergent career paths, continually coming back to the
idea of scaling the cdcn's research. Impacted by Gary's experience
and the rise of AI data aggregation, they saw new
potential for revolutionizing their approach to repurposing medicines.
Speaker 2 (28:31):
And so Grant and I spent a lot of time
thinking about could we start an initiative, an effort to
try to unlock more uses for fdapproved drugs. In about
two years ago is when we launched this nonprofit called
every Year, and we are on a mission to unlock.
Speaker 3 (28:46):
The life saving potential of every FDA approved medication to
treat every disease that it possibly can. There's nothing more
motivating that seeing a patient that is now able to
be with their family and live their life to their
fullest because of the science that you did. It's an
amazing thing that you get to participate in. And so
(29:07):
that's always the sort of the guiding light, the north star.
Speaker 1 (29:13):
So David how did Gary's case play a big part
of the evolution of every cure?
Speaker 2 (29:20):
You know, my book's called Chasing My Cure, because of
course this all started out well, even before Chasing My Cure,
it was obviously witnessing my mom's battle, but this all
really started with Chasing My Cure. And I've said before
and I really believe it, we should have called it
Chasing our Cure, because, as you know, and as you've
heard us discussed, there were a lot of people part
of us. It was actually not me, it was a
lot of us, But it started out that way. But
(29:42):
then for every patient like Gary, for every patient like
Kyla who's getting ready to go off to college because
we discovered a drug to save her life just before
she would have passed, and patients like Joseph who right
now is recovering after we found a drug to save
his life just a few months ago. Each one of
those patients has just led us to say, we are
(30:03):
so happy we did this for them, But how many
more they're out there?
Speaker 3 (30:06):
And what began to dawn on us throughout the years,
because my career went off into the world of machine
learning and AI, was that the way to unlock this
problem that we have been able to start as a
business is potentially to use artificial intelligence and structured as
a nonprofit, and that was really what unlocked our next
(30:30):
sort of journey, which was become every cure grant.
Speaker 1 (30:34):
It's brilliant, it really is. A lot of people are
frightened by AI, but I can't think of a more
wonderful way to utilize it.
Speaker 3 (30:44):
This technology could be utilized in maybe a different context
that maybe instead of focusing on one drug and one
disease at a time for a company, maybe we could
widen the lens. Maybe we could look across all diseases
and all drugs and find the interconnectivity between them to
(31:05):
figure out which drugs should work for which diseases.
Speaker 1 (31:08):
With all the conversations and fear around AI and its
evolution upending certain industries, it's heartening to see a powerful
and potentially transformative application to save people's lives and offer
different treatment options for rare diseases.
Speaker 2 (31:25):
Over the last few years, even just the last two years,
there has been so many advances so that whereas what
we used to do in my lab, where we would
study Castlin disease for example, or related diseases, you know,
we spend years working on a proteomic study or sequencing study,
for example, years to come up with an insight. We're
really proud of the progress we've made. But now utilizing
(31:48):
artificial intelligence, we can actually apply AI to the world's
biomedical knowledge.
Speaker 3 (31:53):
And we would talk all the time about what is
the potential here, what is the potential to scale what's
happening in lab by doing it in the data and
then doing it beyond just one drug and one disease
at a time, And we would check in on this
every few years. Twenty sixteen, it wasn't really possible to
think as big as we were thinking. The data just
(32:16):
wasn't there, And it really wasn't until the last few
years that it started to dawn on us that maybe
something truly was possible here. So ultimately, what we do
is we compile every kind of data that exists in
the world that might be able to link one biomedical
(32:36):
concept to another. So does a drug hit a target,
where is that target on this protein, what gene generates
that protein, what pathway does that protein sit in, what
cell type, what organ system.
Speaker 2 (32:51):
Of course, the predictions are not going to be perfect,
and we're not going to say, oh, just because it's
number one on our list, it's going to work for everyone.
We still need to do clinical trials to validate it,
but the ability to focus in on all the possibilities
to the ones that look most promising is just something
that's never been possible before in human history.
Speaker 1 (33:09):
Grant, what are you most proud of in terms of
every cure?
Speaker 3 (33:14):
I think I'm most proud of the fact that we
have not let this go. And then I'm so proud
of the people that come and join our team. These
are some of the smartest people in the world that
could have higher paying jobs, that could be in Silicon
Valley doing other things, and they are compelled by this mission.
(33:37):
They're compelled by the ability to relieve suffering and save lives,
and they're compelled by the opportunity to create an engine
that should outlast us and will save lives in perpetuity,
whether we're working at every cure or not. In the future,
we want to create something that lasts in something that
(33:58):
has major impact.
Speaker 2 (34:00):
Over fifteen drug where we've identified in or advanced a
repurpose drug for a disease they weren't intended for. And
I'm so proud of that.
Speaker 1 (34:08):
Through the work at the CDCN and every cure over
the past ten years, David and Grant have tirelessly worked
to prevent others from enduring the suffering of orphan diseases.
David and Gary were both on the brink of death,
told there was nothing left to do, just to find
out that a medicine that already existed could be the cure.
(34:30):
Despite having every reason to give up, they persevered, Gary,
what do you want people to take away from your
experience and what got you through it?
Speaker 4 (34:41):
Well, that's a toughye. So through the CDCN, I try
and act as an ambassador to other people who are
facing Castle and disease and just let them note that
they're not alone. It was right after my last round
of chemo and the second FLARE that I attended the
first Patient Loved One summit. I was in a room
full of sixty people who had Castle of disease or
(35:04):
who had a loved one who had Castle and disease.
And so when I talked about that sense of having
felt singled out and being punished, that was the polar opposite.
That was a huge turning point to be around other
people who they're describing things, and I'm like, yeah, I
get that. So that was a big thing for me
to really learn to enjoy connecting with people. And you
(35:25):
just have that sense of other people being with you.
You fight better when you have somebody by.
Speaker 1 (35:31):
Your side, especially someone like doctor David Fagenbaum. I have
to tell you it is such a comfort to me
to know that people like you exist. And I am
deeply indebted to your mother, thank you, and to your father,
your sisters, to Caitlin, because anybody who has gotten you
(35:55):
through what you've gone through to make it possible for
me to be sitting and talking to you today honestly
in their debt and the world is too. I don't
say that lightly. What do you want people to take
away from your story, from your personal challenges?
Speaker 2 (36:12):
I think the things that immediately come to mind are
that no matter how tough things get, no matter how
low the odds are, no matter how difficult things are,
I think just realizing that there may be a path
out of this. At the same time, I think it's
also important emphasize that the path out isn't necessarily going
(36:35):
to be delivered on your door, and that for me,
the reason I'm alive is not because I got really
lucky multiple times. It's because I had the right circumstances
around me, the amazing family, the amazing support, and I
started taking action. And that doesn't mean that anyone who's
dealing with illness or death needs to start experimenting on
(36:58):
their own blood samples or starting a grief organization. But
it does mean that you need to take action in
ways that makes sense for you. And so that might
be getting involved with the disease organization for the disease
that you have. It might be driving in your car
to the world's expert because, like you know, your local
doctor isn't doing what you need. I do think it
(37:18):
takes action.
Speaker 1 (37:21):
If you'd like to find out more about the work
Grant and David and the rest of the team at
Every Cure Doing, visit Everycure dot org. They emphasize the
importance of raising awareness and donations as the best way
to support their ongoing efforts.
Speaker 4 (37:36):
My name is Gary Gravina, I'm David Fagenbaum, and I
fought Casselman disease for nine months.
Speaker 2 (37:43):
And after nearly dying five times in three years from
a deadly disease called Castleman.
Speaker 4 (37:48):
Disease, David Fagenbaum and the CDCN came up with a
regimen that has held me in remission. I've now been
alive for over ten years, for almost eight years now.
Speaker 2 (37:58):
Thanks to a drug that I discovered that I had
been sitting on my pharmacy shelf all along, and now
I'm on a mission to try to find as many
more uses of existing drugs as possible to save as
many lives as possible.
Speaker 1 (38:12):
Next week on Symptomatic, we dive into the modern landscape
of prostate cancer and care. We'll explore emerging therapies, new research,
and some of the biggest hurdles faced by both patients
and healthcare professionals when trying to fight this deadly disease.
We're also excited to announce that Symptomatic will return for
a full season later this year. Thank you for trusting
(38:36):
us to share your stories. If you've experienced a mysterious
diagnostic journey or have a story of interest you want
to share, reach out to us at Symptomatic at iHeartMedia
dot com and keep an eye on your feed Until then,
Stay well. Symptomatic Medical Mystery Podcast is a production of
(38:56):
Ruby Studio from iHeartMedia. Our show is hosted by me
Lauren breg Pacheco. Executive producers are Matt Romano and myself.
Our EP of post production is James Foster. Our producers
are Sierra Kaiser and John Irwin. And this episode was
researched by Diana Davis
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