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