Um, if you'll just start by saying and
spelling your first and last name Phillip
Popovitch PHILLIPPOPOVICH, and how would you
like to be titled?
I guess doctor Popovic?
OK, and you are with OSU
Wexner Medical Center. Yes, OK,
so tell me about this research with mice.
I boiled it down in my head and you
can tell me if I'm right or wrong.
But basically this widely used pain
medication has been found to be effective
in mice at not only managing symptoms
that come from spinal cord injuries,
but maybe stopping the ripple
effects in their tracks.
Is that correct?
Yes, yes and no. I think that that.
Maybe the easiest way to explain it is
that the drug that we tested is a drug
that's used very very often in people.
In fact, it's one of the most widely
prescribed drug medications in people.
In general it's it's widely used
to treat neuro pathic pain.
OK, so if you've ever had
any type of pain syndromes,
gabapentin is a drug that you may have
have been prescribed by your doctor.
In people with spinal cord injuries,
it is often used to treat neuropathic pain,
because that's a complication that usually
develops after a spinal cord injury.
But typically you don't get the
drug until you get the paint right,
so it's it typically is months or
sometimes even years after the onset.
After you suffer the spinal cord
injury that you prescribed the drug.
What we know now that we didn't know
when Gabapentin was first developed
as a drug is where it acts on cells.
The molecular target, if you will.
And what we've just not our lab
didn't discover this,
but others have shown that this drug,
gabapentin binds to a specific
protein found on neurons.
OK, so these are the cells that can
you make the electrical communications
within your brain and spinal cord
that help you move,
think, walk, etc.
When gabapentin binds to this protein,
it is effective in slowing
the neurotransmission or the
communication between the nerves
that ends up causing the pain.
It also we've now understand
when it binds to this protein.
It also keeps synapses from forming.
So what are synapses?
Synapses are essentially little
molecular handshakes between neurons.
Neurons talk to one another through synapses,
and when gabapentin is bound to
this protein on these neurons,
it keeps new synapses from forming.
So after spinal cord injury,
one of the reasons that pain develops and
a lot of other secondary complications
develop that involves what's called
the autonomic nervous system.
So cardiovascular problems,
immunological problems, part of the
reason those problems develop is because.
In the spinal cord.
These synapses increase in number,
and they form new pathways
to communicate right,
and those new pathways are abnormal pathways.
So they're creating this circuitous
communication network that leads to problems.
OK,
harmful problems with gabapentin does
if we can get it in there early.
OK,
before these proteins come up to cause
these these new connections to form,
we can block them and so that's
what we found in the mice.
Is that if we take gabapentin
don't treat animals after they've
developed symptoms but start them
early because we know they are
going to develop them if we get
the gabapentin in there early,
we block these bad harmful neural
connections from happening and we're
able to at least reverse cardiovascular
dysfunction or not reverse it,
but actually keep it from happening.
Keep it from developing an.
We also are able to block
the immunological deficits or
suppression of the immune system
that happens in spinal injured
animals. So these same
things happen in people,
cardiovascular dysfunction,
immunological dysfunction, pain.
All these things happen in people
with spinal cord injuries.
Same thing happens in our mouse models.
So we are basically proposing now that
here's a drug that exists in the clinic.
Given to people widely safe
to use all the time,
but it's usually given after the fact.
So one symptoms onset starts were
saying if you have a high level
injury and you have a serious severe
spinal cord injury and you are at
risk to develop these problems,
why not give gabapentin early and block them?
Keep them from happening.
It may be that we're able
to prevent all these.
Secondary consequences of spinal
cord injury from happening in people.
Is this considered groundbreaking
and what does this mean for
patients? Well, I mean,
I think it's I don't know that it's
going to be considered as groundbreaking.
I think it's a significant
change in perspective on a
longstanding medical treatment so.
If you asked any clinician
who prescribed gabapentin.
What do you think about the the
idea of using it in a different way
to prevent as a preventative drug,
rather than as a treatment?
They they would think that is a.
I would think that they would
think that's a paradigm shift.
It's a new way of using the drug in
a way that could significantly change
how people are treated and how they
respond to their spinal cord injuries.
Why is this so important?
Why is this so needed?
So people with injuries,
spinal cord injuries,
the complications that they suffer
as a secondary consequence most of
the time you if you see somebody
in a wheelchair, you think.
They can't walk there are,
you know there paralyzed and that's true,
but that is usually not one of
the bigger problems that those
individuals are suffering from.
They have a lot of other complications
that are more silent to you and I,
but to them are the things that cause
them to become rehospitalized or
that cause them to die prematurely.
So things like secondary infections
as a result of immunological
dysfunction or immune suppression,
autonomic dysreflexia,
or an abnormal cardiovascular
reflex which involves.
Very high blood pressure
changes that are unregulated.
Those things can lead to hospitalization.
They can also cause a variety of other
problems that can kill the patients.
So keeping that circuit from forming.
Keeping those neurons from causing those
harmful changes can keep people alive.
Keep them out of the hospital and give
them a much greater quality of life.
Just to clarify what part of the research
was conducted at OSU, if any part of the
research, all of the
research was done at OSU,
we have some collaborators on
there who provided reagents or.
Analytical skills, but all of
the research was done here.
What's the timeline? How soon
what happens next? Well, I
think what happens next is so
gabapentin like any drug has the
ability to influence other cell types,
and it can have off target effects.
It can have side effects,
and so I think that one of the things
that we're working on right now is
to try to figure out how long after
the injury can we wait to start
the drug and still have the effect,
because there is what we would
call a critical window.
During which time treatment
or preventative treatment with
gabapentin is going to be effective.
If we wait too long,
those harmful connections may
form and then we can't block
them anymore with gabapentin,
so we're still trying to figure
out what that treatment window is.
Not translating that into
people will be the next step.
What is going to be an equivalent
time window post injury?
Because time window in mice
may not be the same as humans.
In fact,
it's unlikely to be the same in humans.
A mouse lives about two years, right?
And so they have a very
accelerated time window,
which means you know if we're safe and giving
animals drugs within three to seven days.
That may equate to four
to six weeks and people,
so it's it's hard to know that
without actually testing it,
so my hope.
Is that once we can workout a little
bit more and understand how the drug
influences cells outside the nervous system?
Maybe in your bone your liver,
because there is some evidence that
the drug will affect those organs.
If we can prove that it's not
causing any abnormal effects,
or we can understand how it's
affecting those organs so that we
can manage that during treatment.
Then we can go to the clinic
and say to drop doctors OK,
you should be looking.
Dosing people with drug early.
But you need to monitor Oregon AB&C to make
sure that those stay functional as well.
And hopefully what we can do
is to find a critical period of
time where we can dose people.
Then take them off the drug and
still maintain the protection.
So there's still a little bit of what
we would call preclinical work in
the mice before we're able to say,
alright.
Here's here's a guideline that
you should test in humans,
and then I would guess that it's going
to be dependent upon individual clinics,
how they want to try,
and how they want to test it.
It's since it's already an FDA approved drug,
they would be safe to prescribe it,
and it would be up to them to prescribe
on a case by case basis and test it
within their institution about how
they would like to administer the drug.
My hope is that we get
multicenter studies where.
We get spinal cord injury clinics
across the United States would
be a great place to start.
Where they test X number of patients
with gabapentin in the acute post
injury period and we monitor.
Various outcome measures overtime
to see if we have benefit.
There is some evidence in humans
already the retrospective case studies
where they've gone in and evaluated
data long after the patients were
in the hospital and found out that
patients who were given gabapentin
within the first month after
their injury for whatever reason.
Ended up having better outcomes
in terms of motor function,
so those data actually helped
prompt us a little bit to think
you know early could be better,
but why is it better?
Our study actually shows gives definitive
proof in an animal model that early
actually modifies how the spinal
cord itself responds to the injury.
So fascinating, one last thing.
How common are spinal cord injuries?
Is there a statistic on that?
Yeah, there's statistics,
but none of them are good there.
They are all over the place.
There there's I,
I hesitate to even give you numbers
because there there's so many
different statistical models.
It's it's considered a rare disorder.
It's not a common neurological problem,
but it's a incredibly expensive
problem and part of the reason.
So if you were to compare the cost
of management from a clinical
perspective and then from a hospital
discharge and family perspective,
the societal impact and the cost.
Lack of spinal cord injuries
rivals some of the most expensive
cardiovascular diseases, etc.
And it's because people who get
spinal cord injuries are typically
very young and then they live.
40 fifty 60 years needing
constant medical care needing.
Assistive devices and in it and it not
just the individual who is affected,
it's also the family and the caregivers
who also need to make make sure they
maintain and and the more severe the injury,
the more expensive and the
harder it is to manage.
Doctor Popovic thank you.