do you think causes the largest amount
of combined morbidity and mortality in
the United States today cancer diabetes
heart disease you may be surprised to
learn that is stroke every year 600,000
people suffer I skim ‘extra every 40
seconds
the American Heart Association has said
that a stroke occurs since I started
talking somebody has had a stroke so
what does a stroke look like I’m gonna
make everybody in the room a radiologist
for just a second this is a stroke the
gray part is the normal brain the white
part is the affected brain from the
stroke what does a stroke look like on a
person f a s T fast F for face which is
an asymmetry in your face a forearm a
weakness or numbness s for speech which
is an inability to speak altogether or
garbled speech and T T is time when you
see somebody with F a or s you need to
call 911 to a hospital because with
stroke time is brain every minute 1.9
million neurons are affected
that is 32,000 neurons every second so
even though we have 600,000 people
affected every year by stroke compared
to other diseases until very recently
it’s been the Forgotten illness so what
is there to treat stroke let’s take
patient number one he comes to the
emergency department he can’t move his
arm
he can’t move his leg and he can’t speak
it’s been two and a half hours since his
last known normal they do a CT scan of
his head and there’s no bleed they look
at his strict criteria and he meets the
criteria and he gets a clot-busting drug
called TPA TPA or tissue plasminogen
activator was developed and tested in
1995 and shown to have an impact and
improve people who suffer an acute
ischemic stroke the problem with it is
actually its activity while it breaks up
a clot it also causes bleeding and that
bleeding is in the brain as a result
there is a strict time course at which
you have to give the TPA after that
patient was last known to be normal
initially it was three hours and then it
was expanded to about four and a half
hours not only is there a time
limitation but there is 22 criteria that
if you meet one of those exclusion
criteria you can’t get TPA as a result
of the 600,000 people that suffer a
stroke every year about 60,000 or 10%
get TPA and this was the only therapy
available from 1995 literally until 2015
20 years later and there was a
breakthrough patient number two comes in
with a weak arm a weak leg and he can’t
speak it’s been five hours since his
last known normal so now he can’t get
TPA they get a CT scan of his head and
there’s no blood did you a second CT
which has contrast going through and we
see that there’s a clot right in one of
the major vessels of the brain someone
like me goes in through the femoral
artery goes up the aorta through the
carotid artery gets into that brain
vessel and takes the clot out with a
stent retrievers that’s called a
two hours later that patient can move
his arm three hours later that patient
can move his leg and two days later that
patient walks out of the hospital as if
nothing ever happened
five clinical trials in 2015 showed that
this was an effective means to treat
acute ischemic stroke patients so long
as you have a large vessel occlusion I
either something to go after
unfortunately in 2017 only about 18,000
people qualified to get this so do the
math for me
600,000 strokes every year 60,000
strokes
get TPA and to make it a round number
let’s say twenty thousand strokes
undergo a thrombectomy that’s five
hundred and twenty thousand patients
every year that we have nothing to offer
acutely let’s take patient number four
patient number three now has a weak arm
a weak leg and can’t speak it’s been
five hours since his last known normal
so he can’t get TPA they do a CT scan of
his head and he has no blood and they do
a CT angiogram the CT with the contrast
and there’s no big clot there what can
we do for him so when I was in medical
school I learned about this disease
called von Willebrand’s disease and von
Willebrand’s disease is where you don’t
make enough von Willebrand’s factor you
either don’t make enough of it or the
amount that you make is not made right
and 80 percent of these patients have
what’s called type 1 von Willebrand’s
disease and in this patient population
they don’t walk around bleeding
everywhere but if they were to undergo a
minor surgical procedure or have a
dental procedure they would bleed more
than you were I and I thought hmm then
when I was in graduate school I learned
about these molecules called optimist
and abdomen are single-stranded
DNA or RNA that folds into a
three-dimensional shape binds to a
protein and inhibits its activity the
cool thing about app MERS is you can
design a second RNA molecule
that’ll bind to the first RNA molecule
and turn it off an antidote so what we
did is we designed an Optima that bound
to inhibited vwf and designed an
antidote that could turn it off the
Optima literally mimics the activity of
von Willebrand’s disease but we’re able
to control it with the antidote so this
is how we tested it we took mice and we
created a carotid occlusion a blood clot
and we gave them one of three therapies
we either gave them a negative control
or we gave them TPA which is the
clinical standard or we gave them our
after mer and you can see from the graph
behind me in the silver or gray group
that’s the negative control nothing
really happened and the blue group which
is the TPA group you saw something
happen 25 to 30 percent started to open
up and if you look at the red group or
dare I say scarlet group the optimal
treated group you can see recanalization
to 75 to 80% and that’s 75 to 80% held
through throughout the experiment so
then what we did is we took it a step
further we said okay I wonder what the
carotid arteries look like and you don’t
need to be a pathologist to appreciate
that in the control group you had
complete occlusion in the TPA group you
largely had occlusion but in the abdomen
treated group the vessels were wide open
we took it to a third step then and we
tested the animals who got our app de
mer and then who got the Optima and then
the antidote and when we tested them the
animals that got the apt mer and then
the an adult
look like they had never received any
drug at all so I want you to understand
one thing this type of science and
research does not get done in a vacuum
it requires protein biochemists RNA
biochemists animal modelers veterinary
scientists all coming together the idea
of translational science which is taking
a scientific principle and applying it
to a disease process in order to achieve
a therapy that has a beneficial outcome
to patients is team science and this
story hasn’t been written yet completely
as we move to preclinical and clinical
trials we will need pharmacokinetics
specialists pharmacologist clinical
trial specialists by bio statisticians
all to make this go forward now dream
with me for a second my drug makes it to
clinical trials and is successful and
treats a fraction of the population that
suffers from acute ischemic stroke and
patient number four comes into clinic
and it’s been two weeks since his last
known normal and he can’t move his arm
and he can’t move his leg and he can’t
speak and his daughter is with him at
the clinic appointment and she says
doctor well my dad ever speak again will
he ever walk again it is important for
us to realize that we need to go outside
of our own silos and scopes of knowledge
to come together and work towards
solving problems in as complex as stroke
in order to be successful and when I
look at patient number four and I look
at his daughter who is actually patient
number five because she follows up with
the next question the fact that this has
happened to my dad will it happen
me I turn to you to answer that question
I turn to you who are the future
biochemists the future physicians the
future brain machine interface
specialists the future biochemists I
want to hear your ideas I need you to
form your teams and work together to
find solutions that will affect patient
number four and affect patient number
five and the five hundred and twenty
thousand other patients that occur every
year so that we can find solutions to
treat this most debilitating disease I
can’t wait to hear your ideas and I
really look forward to working with you thank you