Revolutionizing stroke therapeutics
[Music]
now my grandfather and i have always
been close
from starting out taking naps on his
chest as an infant
to spending every day at his house as a
preschooler and toddler
learning my shapes and colors as i’ve
grown up
we’ve tried to stay close which can
sometimes be difficult when you live
over 700 miles apart from each other
so my grandparents and i we skype
a lot
lot which has allowed me to keep up with
the important things
such as what flavor of ice cream they
each got from dairy queen that day
or how tech support won’t help them with
their computers
keeping in touch so frequently has
allowed me to pick up on some of the
more subtler things as well
for example when i noticed some changes
to my granddad’s personality and memory
as well as some apathy to things he used
to love
with these changes my granddad began to
also have problems with his stability
and began to fall more
now most people might chalk this up to
normal aging
but as a medical student and a
neuroscience phd
i was afraid that something more serious
was actually happening
i was afraid that all of these memory
and personality changes
were actually signs of a greater
neurological base problem
i’m sure we can all sympathize with not
being able to remember where we put our
keys one day
but there’s a difference between that
and being able to remember what you had
for breakfast
i encouraged my granddad to see a
physician and some neuro imaging
revealed that my granddad was
experiencing
tiny restrictions in blood flow to
certain areas of his brain
or small strokes which were resulting in
something called
vascular dementia
now to really understand what was
happening in my granddad’s brain i want
you all to imagine a network of
sprinklers
watering a lawn on a hot summer day you
could see how if any of the sprinklers
became clogged or blocked
the grass in that area wouldn’t be able
to get the water or the nutrients it
needs
eventually over time this would cause
the grass in that area
to wither and die
now that was exactly what was happening
in my granddad’s brain
as certain blood vessels became clogged
or blocked the brain cells in that area
weren’t able to get the oxygen or
glucose they needed
eventually over time that caused those
cells in that area to die
and this cell death resulted in changes
to his personality
his memory and even his ability to walk
now i’ve memorized the signs and
symptoms of stroke
learned how to measure strokes on
neuroimaging and even work to develop a
therapeutic
to help the recovery of stroke sufferers
despite all of this knowledge i realized
how powerless i was to help
all of these hundreds of hours of
research and training
didn’t matter when i needed it the most
because there was nothing i could hand
him and say
here take this this will make it better
instead everything i and others had been
working on in the lab
while promising was still years away
from clinical trial
clinical implementation and making it
into the hands of the patients who
needed it
now my grandad is one of 15 million
people who experience a stroke
worldwide and don’t have time to wait
for a therapeutic either
what’s even more troubling is stroke is
not only
a leading cause of death and long-term
disability worldwide
but it hits us especially hard here in
georgia
if you take a look at the map behind me
no
that’s not a map of waffle house
locations
that’s actually a map of stroke
incidents
see we’re all living in a region called
the stroke belt
where the incidence of stroke is 30 to
50 percent greater than the rest of the
country
this means that 20 000 people in georgia
will have a stroke this year
and one in 18 people in georgia will
have a stroke in their lifetime
as you can see stroke is not only a
globally
devastating disease but it’s affecting
our friends
our families and our neighbors
we have to work together on strategies
to help those suffering today
now the biggest bottleneck to helping
those suffering today
is the divide between therapeutic
development and getting it to the
patients who need it
this divide is referred to as the gap
between the bench
and the bedside this means that while
we’re making great strides developing
new therapeutics and techniques in the
lab
they’re not making it to the patients
who need it
now why does this gap exist
well the drug development process is
long
difficult and expensive first
from drug must complete studies and
animal models
then it must move through three phases
of clinical trials
phase one is safety testing
if no adverse side effects are seen
after a couple months of testing in
human patients
then a drug can move to phase two or
efficacy testing where we ask
does the drug work this phase can last a
couple months to years and involves
hundreds of patients
only about thirty percent of drugs make
it past phase two
in phase three there’s large-scale
testing
in hundreds of thousands of patients
over multiple years
if a drug is one of the 14 that
successfully completes
all three phases of these clinical
trials only
then can it be requested for fda
approval
this arduous process takes an average of
12 years and 1 billion dollars to
complete
now these fda approval and clinical
trial steps are absolutely necessary and
i’m not advocating we do anything to
change them
i am however advocating we make this a
two-fold process
in order to help patients the best of
our abilities present
and future we must one continue
therapeutic development
but two simultaneously work on
immediately
implementable techniques frankly because
people are suffering and dying of this
disease today
and it’s our obligation to help them to
the best of our ability
during my phd i wanted to test out this
two-fold approach in practice
in order to focus on something with
immediate potential i set my eye on
stroke recovery prediction models
while the ability to predict someone’s
recovery after stroke has improved in
recent years
there’s still room for refinement
i wanted to see if we could use narrow
imaging a patient was already undergoing
such as mri and use that to predict
their outcome down the line
now the goal of this work isn’t to
develop something that’s going to
immediately enhance a person’s ability
to walk or talk after a stroke
the goal of this research is however to
develop something that physicians can
use to make
targeted and personalized rehabilitation
plans for patients
in order to make these targeted plans i
took an mri
and made a bunch of measurements that
were related to the brain after stroke
i then looked for the relationships
between these measurements and long-term
outcomes in our models
from this analysis i was able to
identify one measurement out of many
tested
that was significantly correlated to
gait behavior
survival and recovery up to 12 weeks
later
this is pretty awesome we have something
we can easily measure within the first
24 hours of stroke
that can tell us what to expect out of a
person’s walking and recovery
up to three months later and this is
something that doctors can start
implementing for people like my
grandfather
right now
while doing this work i also wanted to
focus on the overarching goal
of this twofold process or developing a
therapeutic
that can aid in the recovery of stroke
patients
currently there is only one fda approved
small molecule therapeutic for stroke
called
tpa now tpa works to break up the clot
think drano for the brain rhino
but it has no direct mechanisms to
preserve protect or regenerate tissue
thinking back to our hose analogy it’s
like finally being able to untangle or
unclog that hose after
hours of decreased water flow
sure it’ll help save some parts of the
dead and dying grass or brain
but for the areas that’s already died
it’s already too late
building off the work of others before
me i worked with my lab mates
to develop a therapeutic with the
potential to heal
this neurological damage this
therapeutic
called neural stem cell-derived
extracellular vesicles
or nsevs are nano-sized packets of dna
rna and protein instead of just working
to reopen the hose
like current approved therapeutics with
these nsevs we’re actually
reseeding parts of the dead and dying
lawn
to salvage what used to be there and
encourage new life
from our experiments we’ve seen that
these nsevs
not only decrease the damage done from
stroke but actually
improve the speed of recovery and even
large detrimental strokes
to really illustrate this i have two
videos to show you
in our large animal pig model of stroke
the first video is of me and an animal
three days after stroke
this animal has not received treatment
for this testing we want the animal down
a track which measures property of their
gait
or walking such as their pressure speed
or stride length
as you can see this animal needs a lot
of encouragement from this rattle to
successfully walk down the track
in contrast here is an animal three days
after stroke
that has received these nscevs or
seeds
as you can see there’s a perceptible
difference
in the speed of recovery of the animal
that has received the nscevs
compared to the animal that hasn’t
based on these experiments we believe
that our nsevs have promising potential
to help the recovery of stroke patients
worldwide
now i truly believe this two-fold
approach
of continuing therapeutic development
while also simultaneously working on
immediately implementable techniques
will be one of the keys to providing the
best care we can for patients
but there’s one last part of this game
plan i’ve left out and that’s step
three or you
see stroke has been a devastating
disease for a long time
and i’m sure you’ve all been personally
affected by it
due to limited success in clinical
trials however funding agencies and
individuals
have started to lose hope in the
possibility of finding a cure for stroke
we want to reinvigorate the field to
believe in techniques for today while
continuing to work towards a cure
for tomorrow in order to bring about
this change
we need your confidence support and
participation
this work is only possible through your
endorsement so we’re actually
asking you to show your support vocally
and monetarily
speak out on social media in
conversations with your communities
through political advocacy and through
contributions to research drives and
taxes
through your passion and support we can
bring awareness to the need for more
stroke research
together through this raised awareness
of stroke and multifaceted research
approaches we can start to re-landscape
the field
maybe one day we’ll be able to talk
about life after stroke
not in months and years of rehab
but maybe in days and weeks
not as a completely debilitating life
event
but as an unfortunate setback
we can start to restructure the emphasis
from an all-or-nothing game of
therapeutic development
to an all or something game that can
help patients today
frankly because i want my granddad back
i want him back to his happy healthy
jokester self
and i want to be able to hand him
something that can make it better before
it’s too late
and i want the same for all of your
loved ones and grandparents
and maybe after today we’ll be one step
closer to making that a reality
thank you