Hello, and welcome to the Physics World Weekly
podcast.
Heart failure is a serious condition
in which a damaged heart
loses its ability to pump blood around the
body.
The damage usually gets progressively
worse
so that 5 years after a diagnosis,
about 50%
of patients
with heart failure will be dead.
The disease affects as many as a 100,000,000
people
worldwide.
And in the UK,
about 1 to 2 percent of the National
Health Service budget is spent on managing the
disease,
with most of the expenditure
related to hospitalization.
So it's not surprising that scientists
are looking for new ways to improve the
outlook for people with heart failure
and perhaps even cure the disease.
This podcast features the biomedical
engineer,
Stuart Plant,
and the physicist,
Ashok
Chowhin,
who work for Sirix Medical,
a UK based company that's developed a bioelectronic
system that helps patients with heart failure.
Stewart is the company's CEO,
and Ashok
is its senior scientist.
Here they are in conversation
with Physics World's Margaret Harris.
As well as chatting about the company's work
on treating heart failure,
Ashok and Stewart also talk about other applications
of bioelectronics
and the challenges and rewards
of developing
medical technologies
within a small company.
Okay. So
first question, Stuart.
What medical problem is CERiX trying to address
here?
Well, the first,
medical problem we're looking to address, and there
are actually multiple
applications
for our technology. But in the first instance,
we're looking at a disease called
called heart failure.
Now heart failure occurs when you've had,
you know, heart attack, you've had chronic hypertension.
Maybe, you know, these days you have to
think about COVID
and infections that that can affect the the
muscle of the of the heart. But basically
some incident has caused caused damage to the
heart and the muscle
has been has been damaged. Some of it
may have died. Some of it has become
dysfunctional
or at least immobile,
but your heart basically can't work as, as
well as it, as it once did.
So it means that it's not supplying as
much blood to the body
and your body doesn't like this. So it
kind of
activates various compensatory mechanisms. It will push your
blood pressure up and increase the volume of,
of, of fluid basically
in your body. And it will cause your
heart to beat harder and it will cause
it to be beat faster.
Now this is one of the nature's quite
good at these types of mechanisms. And it
does, it does provide compensation for that decrease
in cardiac output from the, from the damaged,
damaged heart. So it is kind of restoring
its blood supply. But now you've got a
heart which is damaged already, which has been
made to work harder.
And as with any muscle, if you don't
rest it, once it's been damaged, the the
injury just gets worse.
So heart failure occurs when the body reacts
to this initial initial injury
and drives the heart on. And then over
a period of time, that injury just gets
worse and worse and worse. And the structure
of the heart becomes
more abnormal
and the function of the heart just becomes
poorer and poorer. And what this means for
patients is that eventually they start to experience
feelings of breathlessness. They can't exercise in the
way that they once they once did. But
as the heart gets worse and worse, eventually
you can't even get out of a chair.
Making a cup of tea becomes exhausting exhausting.
And ultimately, these patients, you know, they end
up on oxygen 24 hours a day. They
end up in bed.
They end up in hospice care. And then
unless they get something extreme like a heart
transplant or maybe a,
an LVAD heart pump device,
ultimately, they'll they'll sadly, they'll die.
So at the moment, there's about, you know,
if, I mean, if you Google it, it's
it says that there's about 30,000,000
people in the world with with heart failure.
That's a bit of a European
US centric
number, right, I'd say. I mean, on average,
there's about 2% of the adult population has
heart failure. So it's probably more like a
100,000,000 people worldwide
currently have heart failure.
And the survival rates for these patients are
pretty poor. So on average,
5 years after diagnosis, 50% of the patients
with heart failure
will be dead. And in fact, in the
1st year, 30% will will probably die
after the initial diagnosis.
Moment the, you know, medications are directed towards,
you know, trying to control the symptoms of
heart failure. So they'll try and, you know,
give you a better quality of life, improve
your exercise tolerance. And a lot of them
are trying to, you know, maybe slow the
heart down. They give you beta blockers, slow
the heart down. They'll give you ACE inhibitors,
dilate your blood vessels. And that's trying to
relieve the strain on the heart. So trying
to release the extra strain on the heart
and try and prolong
the, the lifespan of the, of the heart
itself. But they're not really getting to the
core of the disease itself and trying to,
trying to treat
and basically reverse and cure this disease.
And that's why Ceryx is, is a, is
a bit different.
So you've talked a little bit about what
the existing treatment is in terms of oxygen,
ultimately a heart transplant or a physical device
to help the heart continue to beat.
How is Ceryx's technology different from that? How
is your solution different from that, I should
say?
Well, CERECS came to this problem, I I
suppose in a bit of a convoluted way,
really, to be honest. I mean,
I I I we're 2 academic founders. 1
was a cardiac physiologist in Bristol, and he
was studying a phenomenon
called respiratory sinus arrhythmia.
Now this is a natural synchronisation between the
heart and the lungs. Your heart and the
lungs are linked. So that when we're, when
their system's healthy, they'll work together to optimise
the performance of both of those organs. And
put simply, when we, when we breathe in
our hearts accelerate, our heart rate goes up
very slightly. And when we breathe out, our
heart rate goes down very slightly.
Now it'd been known for us, you know,
it's a couple of 100 years since this
phenomenon was first identified, but no one really
examined as to why, why the body would
bother to do this.
More recently in the, you know, the recent
decades, people have started to look at why
this phenomenon occurs and have discovered that it
actually brings quite a lot of benefits to
both organs.
So most obviously, you know, when we breathe
in our lungs fill with oxygen, so our
heart accelerates to to to pump as much
blood as possible around the lungs to aid
with the gas exchange.
Also, you know, our lungs are in our
chest. When we breathe in, we lower the
pressure in our chest to allow the air
into our lungs. Of course, our heart is
in our chest as well. So now the
heart's in beating the lower pressure environment, so
it takes less energy for the, for the,
for the heart to be.
And now there's a growing body of evidence
in the literature around, you know, the all
these little benefits that RSA bring to their
cardiovascular assist, cardio respiration.
Now Julian was looking at well, he was
looking at this phenomenon in itself and he
was also looking at the
we have this RSA when we're young and
healthy and we it's enhanced in athletes. It's
also present in all vertebrae animals. So even,
you know, even fish display some RSA type
mechanism.
You know, so that when we get diseases
like heart failure, you lose this, this RSA
mechanism, the synchronisation between the heart and the
lungs. So Julian's hypothesis was,
if you could put RSA back into patients
with RSA, would it restore the benefits of
this mechanism and could that potentially be therapeutic?
And the problem Julian has was that restoring
this link is actually bit of a more
of a complicated problem than it than it
might first appear.
But fortunately, he
he kind of received an email from a
physicist at at Bath University,
who is looking at synchronization between nonlinear oscillating
systems.
Now
where you get a lot of nonlinearity
is in is in biology. Biology seems to
love nonlinearity.
So although it's not a natural place for
maybe a physicist to be looking, they they
tended to look towards biology and looked at
things like your legs. Your legs to a
physicist in in in in their field would
is just, are just a couple of oscillators.
Not linear oscillator, like, but it's keeping synch,
allow us to walk and then to run.
And how is the body able to to
do that? How are we able to change
our gait? How are we able to go
from walking to running, trip on a stick,
and actually not fall over? And I suppose
it is is an interesting physics problem.
So So the physicist in question was Alan
Nogaret at Bath and he had, you know,
been studying this for some time and had
come up with,
basically,
a paper, an electronic representation
of the MEC control systems that the body
uses to control these nonlinear oscillators.
And now he had these devices and he
sent out a blanket email, I think, to
Bath and Bristol University saying, I've got this
technology. Does anybody have any ideas of what
I should do with it? Now, fortunately,
Julian saw the email, got in touch. And
that's really how how, Cerrits came about.
So we spent, you know, that, that was,
well, I always started from 2016, but I
think those guys have been working on it
prior to, to that. But we've spent since
about 2016, trying to develop Alan's technology into
something which we could eventually use
to re,
reestablish this connection between the heart and lungs,
restore RSA.
And at the moment we're trying to identify
whether,
whether doing this has a therapeutic effect on
patients with heart failure.
Okay. I wanna bring in the ASH Lock
here. You know, can you tell us a
bit more about the technology and how that
actually works?
So as Stuart just touched on the respiratory
sinus arrhythmia,
how it is beneficial
to the body, and
you
find that in healthy,
humans.
But in heart failure, that respiratory sinus arrhythmia
doesn't exist.
And another aspect of,
respiratory sinus arrhythmia is that, heart rate variability,
which is a good sign, again, present in
healthy humans.
So that heart rate variability is lost in
heart failure in patients.
So our technology, what it does is it
mimics
neural networks
in the body,
called central pattern generators,
and these neural networks have specific tasks. They
can generate rhythms
without rhythmic inputs.
And so, our electronics basically emulates
those neural networks,
and it generates rhythms,
in coordination with restoration,
and
other,
inputs.
And it does it breath by breath
Okay. To provide those subtle,
respiratory sinus arrhythmia.
And we we re so this way, we
reinstate
the healthy respiratory sinusoid pneumonia in the heart
failure patients.
And
the,
physiological
improvements
found was the increase in cardiac output by
about 18 to 20%
in the heart failure.
Just to give a reference, 3% is considered
significant.
So, yeah, if you if you could put
this in a pill form, it would be
flying off the shelves and selling out. Yeah.
So what does it actually look like in
a patient? I mean, I guess you've you've
done some animal studies so far?
Yes. So the studies have been done in
small animals and large animal models.
And in both cases, we had similar amount
of
increase in the cardiac output.
And,
so in the the initial
prototypes of the technology were just the electronic
circuit on board and
the trialed,
in in the labs. But for the large
animal trials,
these were,
again, in the static conditions in the lab.
So
what we're now trying to do is make
them,
we've got an external,
pacemaker now. So and then the next stage
is to make implantable,
pacemaker out of this. And
the electronics remains the same, but it shrinks,
of course, a bit. Okay? Yeah. So you
you've got potentially something you would wear on
the outside, and then the next step is
to make it so you can actually implant
it. Implant it. Yes. I see. Okay.
And you told me a little bit, Stuart,
about how the company got started. How did
you get involved in it? Because you're you're
not you're not one of the 2 sort
of the physicists and the physiologist,
or clinicians, founders.
I had I had kind of an interesting
job. I mean, I'm a I'm a scientist
by background,
but at the time I was working for
a company, it was essentially a a venture
capital investment company.
Now their USP
at the time was that they had relationships
with universities
and they signed contracts with these universities, which
would allow them to go in and meet
the academics,
look at the, research that they were doing,
look at the IP that they were producing,
and then they'd have kind of first dibs
on potentially investing in that technology
and, and, and, and spinning it out, essentially.
So my role was to, I was the
guy that went into the, into the university.
So part of my patch within the, within
the UK at the time
to the Southwest and some of the London
universities. So I'd go in all these universities,
meet everyone and anything like the look of,
I'd take it back to IP group at
the time and,
you know,
pitched that we should, we should be backing
this technology.
So when I saw, when I saw this
technology in 2016, I, I, it was, I
mean, it was, I mean, I say this
now, but I mean, it was the best
thing I I'd seen with the universities. I
mean, this is
the the RSA,
as a therapy for heart failure in itself
is is massively exciting. You know, this is
it is one of the big healthcare challenges.
The expenditure on it on the heart failure
is is, you know, it's only comparable by
with cancer, to be honest, at the amount
it costs that the health systems at the
moment.
And it's
as with any disease, I suppose, you know,
the world's getting older, the oil's getting fatter,
and the problem's only getting worse. So that
in itself is a is a is a
big target. But the technology underneath is interesting.
I mean, I'm not a physicist by background
and I admit that, you know, I still
struggle with with some of that
with some of the theory behind how our
devices
our devices work, I could comprehend enough to
see that this actually had the potential to
be
really a new approach to medical devices more
more generally. I mean, I think as Ashok
was saying and I was mentioning earlier, I
mean, it it really does look at biology.
How does, how is biology able to control
the complex processes that go on within, within
the system?
Within the, within the body.
And medical devices up to this point, we've
kind of taken you know, electronic technology. So
the same technology in your phones or your
computers.
And we kind of impose that on, on
the body. And the 2 things don't communicate
very well. One's
a basic level. One's a digital system,
communicating ones and zeros.
One is a very complex analog system. So
everything's, everything's 1, no everything
in between.
And the, and the body, that's how the
body functions and trying to control that process
of trying to correct biological processes using digital
system in some ways, doesn't really make sense.
So when you first saw what Alan and
Julian were doing, you go, well, actually that
makes sense. That's a sort of seamless connection
between the human body. You can feed,
biological signals into this technology and it can
process it as part of its natural, natural
functions. Whereas, you know, digital systems, you've got
to take the, take the biological signal, you've
got to filter it, you've got to process
it to enable it to,
to maybe to feed it into the, into
the medical device itself. And what that means
is you get very crude, you get very
crude systems. I mean, most medical devices at
the moment, a bit harsh,
they just
electrocute.
They just electrocute in every of the body.
I mean, the pacemaker today, you just get
60 electrocute
the heart 60 times a second, 60 times
a minute rather to control rate. You know,
Parkinson's disease brain implants, it's mostly just as
simple
stimulation in particular area of the brain. There's
not a lot of complexity there. There's not
a lot of feedback.
So I thought that, you know, this first
application in heart failure is incredibly exciting, but
there's more to it there. I think that,
you know, further down the line,
certainly Ceryx's more biomimetic approach, create
mimic the systems that they're trying to to
control, makes makes a lot of sense.
And that's kind of the premise that that
it came from. So I, yeah, getting back
to your question, I mean, I, I, you
know, I found the technology in 2016. I
continued to work for IP Group. We, we
did some early investments into, into CEREC after
we spun out of, of Bath and Bristol
Universities.
And then in 2019,
say IP group, you decided to take a
different route. It's got moved away from the
university model. They didn't want to, they couldn't,
can we work with the universities in the
same way they had before? So when they
went off in that direction, not I stayed
behind, and I left IP group and and
joined CEREC full time.
Yeah. That's how I came about.
And, Ashlag, you you are a physicist by
background. How did you get interested in this
this technology and and get involved in helping
to make it it work? So
I was a doctoral student of professor Nagar
in University of Bath. And, when I was
finishing my PhD, there was
a this project had,
was going on. And so there
was
a position for postdoctoral
researcher in in that group,
on that project. So
I found it fascinating. So I joined the
project, and I spent few years
developing actually the
hardware and
the technology and working between the labs labs
of professor Norbert and professor Julian.
And what was the most difficult part of
that task instead of developing the technology?
As there are 2 different disciplines involved, there
are challenges from both disciplines. 1st was,
actually making the
hardware designs and studying the dynamics that will
be,
dynamics of the network that will be more
useful in coordinating respiration and heartbeat.
And then
bring bringing it, for physiological application and actually
saying,
for example, tuning the parameters
and the range and the rate of adaptation,
those kind
of technical details that you have to work
out from the scratch in in a different
lab, which is physiology lab. And I wasn't
a a physiologist from background. So it was
a learning process
on 2 different levels,
but, eventually, we got there.
And, Stuart, what will you say in terms
of what was the most difficult challenge you
had from the business side of things to
get this this company to where it where
it is now?
I'm not sure. I put I should put
this out in a in a podcast, but,
I mean, the the biggest problem for any
any start up is always funding.
It's so
so much effort is put into just, just
feeding
cash into,
into, into the business. I mean, we're, we
Ceryx has been quite,
efficient, I think in the way that he's
done things. You know, we've got a very,
we've got a small but highly
experienced
team.
We've also been quite smart in how we've
been using sort of external subcontractors just to
kind of keep sort of overheads overheads down
and proceed as, as efficiently as possible.
So our cash requirements have been kept to
a minimum, but it's but it's just been
so difficult to to raise the to raise
the money. I mean, one of the things
that you want to do
with any
development program is is to keep momentum. You've
got to keep pace up.
And sometimes
doing that alongside
funding timescales
is just really, really hard. I mean, on
the one hand you have, you have grants.
Sometimes they have like ludicrous
process which can take, you know, 12 months
or so.
And, you know, that just doesn't fit with
a fast moving,
startup. You know, we've, we've 12 months' time,
we'll have we're
in a completely different place than where we
were 12 months ago. Trying to plan that
ahead is quite difficult.
Investment
in the account I mean, I think that
we, you know, we were unlucky, I think,
in that, you know, when we really started
to move around sort of 2018, 2019, we
started getting into the sort of pandemic type
period
and then everything became a lot more difficult.
Funding became a lot more difficult. I mean,
even now,
you know, investors tell me that they're having
difficulty raising money. So us raising money from
then, everything was quite difficult.
I mean, we were
we did well. We wrote we closed a
pretty large round,
nearly nearly 3 years ago now where we
we wrote oversubscribed.
But even then, it was, you know, it
was it was a 14 month process, I
think, to to to.
I do think as well that, you know,
working in the space where, that we are,
I mean, investors have a, to be fair,
I mean, I've been one, so I know
that investors have a hard time with it.
They, they look at a lot of technologies,
a lot of companies, there's a lot of
information that they take in. And very often,
you know, they, they they're dealing with the
business side and they come from a financial
background.
And I'll sit them down in front of
a physicist and just go, come on, why
don't you appreciate how brilliant this is? And
it's really hard for them to do that.
But I mean, it is particularly hard, I
think for CEREX because we, as Ashok said,
we encompass so many different aspects. We've got,
you know, cardiovascular physiology,
we've got electronics, we've got physics, we've got
mathematics.
And
part of the beauty of what we do
is in the complexity
of the technology.
It's why, you know, it's why we've been
able to achieve
what we have with RSA with other other
people may not have been able to because
it is, it is quite complex and that's
what's great about it. But trying to communicate
that message in a way that people just
don't
investors in particular, don't just turn off and
just go, no, actually this one's too hard.
I'll look at the next, I'll look at
the next technology. At least I slightly understand
it
is, is a difficult problem. I mean, and
yeah, so
that's my long winded answer to say, yeah,
just, just, just cash. But I think any,
any startup probably in the world will say
exactly the same thing. Just, just sourcing funding
for, for even, it doesn't matter how brilliant
your idea is.
Getting getting cash to fund it is always
the challenge.
And I understand you're you're about to enter,
a new and and differently challenging phase for
the company. You're you're starting your first in
human trials. What sort of challenges does that
bring? Maybe, Ashlag, you wanna go first?
So
some of that are the regulatory
approval we need. It takes a very long
time and longer
document preparation.
And
even before that is the preparation for the
technology
that will be evaluated
for
regulatory approval.
So we
again, then we have to coordinate,
as Sushu said, electronics, physics,
and mathematics, and everything.
And we have to commit to a design
of the technology.
There can be other versions, improved versions later
on, but we have to then commit to
a certain design before
we file for the regulatory approval. So
that was a challenging part from my side,
and I think Stew can add further.
So from from the clinical side, I mean,
we as I said, we've we've been pretty
efficient, I think, in the development. We went
from a we went pretty much from a
standing start to
a,
an MHRA approved class c medical device in
about 2 years, which is pretty good going.
And then we thought, right, we just gotta
just gotta put it on a patient now.
It's all been approved.
And, it actually is been incredibly incredibly challenging.
I mean, obviously, you know, the patients we're
dealing with are really quite really quite sick.
I mean, heart failure is a serious condition.
For this clinical study, we're taking patients who
have got heart failure, who are going in
for a coronary artery bypass
graft operation. Now why we were interested in
these patients is because
these patients as part of standard clinical care
are fitted with an external pacing device. So
when they go in, they go in for
the procedure and just when the surgeons finish,
you'll put a couple of pacing wires, 1
in the atrium, 1 in the ventricle.
And these wires then just come out through
a through a hole in the chest
and a patient is stitched up. And when
they get taken down to the ICU, they'll
they'll have a an external pacing box. And
that just controls their heart rhythm as a
surgeon who recovered from the anesthesia. They can
be at sort of high risk for arrhythmias
there, so that prevents that from happening.
But generally what will happen the next day
is the cardiologist's surgeon will come round.
They'll turn down the pacing on this device.
And if that patient's got a normal sinus
rhythm,
they'll turn that pacing box off. Generally, the
wires stay in for a couple more days
just in case the pacing's needed. But eventually,
the nurses will just come around and they'll
just basically just tug on the wires and
it they come off the outside of the
heart and they'll stitch them up and away
they go. So we were interested there because
that's an opportunity for us to
where pacing is huge without having to implant
the device into the patients. What we've done
for this first study is taken our technology
and integrated it with an existing external pacing
device. So they can be fitted with that
pacemaker when they come out surgery
and just give a normal pacing. And then
when they're ready to come off that pacemaker,
we switch it over and then it gives
them their
delivers RSA pacing. And we'll just leave that
on for the duration that patient remains in
hospital, which is, you know, typically about sort
of 5 days or so. So I'll give
this first indication of the kind of safety
and feasibility of RSA patient in patients. But
maybe also we'll get some early indications of
efficacy.
You know, we're that's what we're hoping. But
lot there's a lot going on there. I
mean, these patients, as I say, these patients
got heart failure. They were going in for
a coronary artery bypass. There are risks to
that, to that, to that operation.
So, you know, getting that ulcer approval as
Assoc Sheikin said is quite challenging, but then
also getting the patients into the study are
quite difficult.
One problem that we didn't expect that we've
found in these early weeks of the study
is that
often
these patients are being admitted to hospital several
weeks before they have their surgery.
Now sometimes they've kind of got themselves in
a bad way because maybe they haven't been
able to manage their diseases as well as
they, as well as they might.
One of our first candidates had quite severe
diabetes
and hadn't been very good at managing that
diabetes. So of course, when they came into
the hospital,
the nurses were all over them. They they
optimized their their their therapy. They monitored their
diabetes properly. And what we found was that
this patient was quite unwell when they came
into hospital. By the time they came out
and had the surgery, they were actually too
healthy to be included in our study. So
it's great for them, but, yeah.
And actually that's happened quite a few times
now. So it was this problem of the
it was basically the hospital was doing the
job too well. They were we're, like, making
these patients well
for us.
And then, you know, occasionally you get complications
from the surgery, you know,
one guy unfortunately got a bit of a
bleed after the surgery, had to be readmitted.
I mean, he was fine after the surgeons
had another go, but, but, you know, it
excluded him from the study. So it's
it's it's a it's an interesting but frustrating
period. You know, as scientists, we used to
set up our experiment and then we do
the experiment. Here we've got, you know, health
systems and patients
and medicine getting in the way and it's,
it's, it's,
yeah. It's
making me call my hair out at the
moment, but we're getting there.
How long has this clinical trial's meant to
last, and then what happens after that?
So we're gonna we're gonna look for a
sort of a we're looking sort of 12,
18 month recruitment period. We've we've actually gone
quite large with, with this study.
So normally as a sort of first in
human evaluation, we go for about sort of
15 patients.
Based on the data we saw from the
preclinical work, we've kind of pushed it to
30 patients
because we sort of
based on the human animal data, maybe if
we recruited that many patients, we might start
to see some, some significant
indications of efficacy in these, in these patients.
Now there's 2 ways that this could go
after, after this study.
We've, we've sort of, you know, this is
a first in humans, so we just want
to show that RSA pacing is safe and
that provides us as a gateway to then
take the next step, miniaturize our technology
and implant it with patients with more straightforward
heart failure,
and then pace them over a longer period
of time. That gives us a much that
gives us, you know, months of therapy rather
than the days of therapy that we're getting
this study.
And then we should get an indication of
the full effect of of RSA therapy.
However,
there is the possibility. I mean, all patients
that go in for, for, for heart surgery
generally have depressed cardiac function when they come
out. The heart's been, you know, your chest
has been open. The heart's been messed around
with its, you know, it doesn't like. It.
So your cardiac output probably is going to
be down for a few days to, you
know, few days to a few weeks post
surgery.
Now with most patients, it slowly recovers and
the patients will feel better as that, as
that comes around.
But there are patients about 15% of patients
where that, that recovery never really happens. And
there'll have to be additional interventions to try
and,
make up for this, this deficit in cardiac
function.
So if we had a device whereby, you
know, these patients are getting pacemakers anyway, if
you fitted them with an RSA pacemaker, we'd
not only protect them against those arrhythmias,
but would also improve their cardiac function.
Would that mean that those 15% of patients
never, you know, get that prolonged depressed,
cardiac function. And also all patients, the quicker
you can improve their cardiac function, the quicker
they're going to recover and the better they're
going to feel. So maybe it would be
a solution for all patients having, having reduced
cardiac,
having cardiac surgery.
So there is there is kind of 2
possibilities for this study. 1, you know, it's
just the, you know, the first stepping stone
in our development for long term therapy for
heart failure, but also potentially it's a new
therapy for all patients going in for cardiac
surgery.
And we'll just have to,
just wait and see. Now I understand that
that, you know, this is you're looking at
at cardiac
applications of this sort of,
you know,
your the core technology in the first place.
Are there any other areas where this, you
know, sort of I guess you could see
appreciation of of the nonlinear nature of the
body signals could and and coupling an external
or implanted
electrical device to that. Are there other applications
where that could also
be effective clinically?
Yeah. So, I mean, if if you know,
just to throw a few examples out there.
I mean, you know, you said, you know,
the body's full of nonlinearity,
and we think our technology will be ideally
suited
to a more physiological control to these mechanisms.
So one area that Ashford's been looking at
is,
a condition called dysphagia,
which where you ability to swallow. And this
most commonly occurs after people have had a
had a stroke.
Now swallowing is is a coordination of about
a dozen muscles within the within the throat,
And they all have to have, they all
have a rhythmical contraction, which needs to be
coordinated.
There are medical device therapies out there for
dysphasia,
but they tend to be, you know, a
single point, electrical stimulation
of the throat or they are special foods
that makes it easier for the for the
patient to to swallow.
Whereas our technology, we're really good at taking
input from those 12 muscles, which were currently
dysfunctional and then coordinate
their contraction into the appropriate rhythm to to
enable swallowing.
There obviously
are the
your di rest of your digestive tract also
is coordinate is a coordination of multiple muscle,
give that peristaltic motion. And there are certainly
plenty of patients out there that have,
problems
with the, lower digestive tract.
The
example that I started with of your legs
is, I suppose, is the most obvious one.
And that's really the kind of
ultimate
application for our technology.
I mean,
Ashok talked about central pattern. Right? Is those
those networks of of neurons in your in
your spine are are amongst the most complicated
ones that we thought we might we might
tackle. But,
I'm a little cat story. I had, people
have told me to stop telling the cat
story, but it's a bit off tangent. But
basically if you go, if you go on
YouTube, there is, and you can find it,
there's a black, grainy black and white image,
video really.
And I imagine it's black and white because
you probably can't do these experiments anymore, but
what they've done to it, they've taken it
out and they've decerebralized the cat. So basically
severed the connection between the cat's brain and
the cat's legs. So you would assume this
cat to be paralyzed, but what they do
is they take the cat and they put
it onto a treadmill. And as soon as
the cat's feet touch the treadmill, it starts
to start to walk and they'll turn the
treadmill up and the cat will start to
run. And they, for some reason, they put
a little trolley on the back of it
and they pull the car. I don't know
the necessity of doing that, but it just
shows that it can change the gait, I
suppose, of, of the animal, even though there's
no connection there between the brain and the,
and the, and the legs. Now I'd always
assume that your brain had something to do
with your ability to walk, but it seems
that you just like where you want to
go and then your legs kind
of control themselves. And the way they do
that is they send sensory inputs up to
the spine, the central pattern generators process that
information, then send the,
the stimulator impulses down to your legs. And
that provides the coordination of the muscles, which
allows us, which allows us to walk. And
that experiment that they performed, which is demonstrating
that the
legs is mediated by
the nerves within the spine, rather than also
the brain. So for us, that means that
someone who's had a,
a spinal cord injury, maybe it's even severed
to the spinal cord, we could set we
could rep
those central pattern generators in the spine and
restore the ability to to walk.
Like Stuart explained,
so these are central pattern generators that control
the rhythms and then stimulate the muscles, and
that generates different gait for the legs. And
if there's somebody's amputated,
and
they can be used to control those artificial
legs.
But the control of arms is even more
complex where you have
different,
fingers and
different grip sizes. So this nonlinear
dynamics of the central pattern generators
can then be used to
control the movement of arms
with different crypt levels. If you imagine the
complexity of the network, it can be extended
by adding more neurons to it.
And this would presumably require quite a lot
of computational power as well.
It would. And if it's to be done
digitally,
but in analog systems,
it can be done much more efficiently,
because it'll be real time,
as it's a nonlinear and continuous time
signals generation.
So the
and lots of parameters are already
defined
so that you, ma'am, you'd you won't have
to look for the
certain level of inputs and then make decisions.
It will be much more dynamic than that.
So that's where the true power of the
continuous systems,
will be in nonlinear systems, will it?
Well
and
so final question for for both of you,
actually. You know,
what do you know now
that you wish you knew when you started
this journey back in 2016, in your case,
Stuart, and when you're starting on your your
postdoc Ashok?
I mean, it's certainly the I mean, there
are some of the boring ones and you
can fill them out. So, I mean, I
think the I think the clinic I think
the clinical side of things has been a
bit little bit of surprise. I mean, I
think that when we when we when we
can we thought the message the biggest challenge
was gonna be the regulatory approval for the
device, but we were actually
pretty pleased with the way with the speed
with which, you know, the the authorities processed,
and evaluated our technology. And that was really
straightforward.
Getting into the clinic, I was warned, I
think, that it would take 6 months from
that point to, to getting the first patient
in, and I didn't believe them.
And they were right. And they were right.
And,
yeah. And I, I didn't appreciate that the
just what is involved with what seemed to
be a relatively straightforward
straight.
In terms of starting out the
I think that it took us a little
bit of time.
I mean, the the thing about our technology
is that the
the clever bit is the is the, you
know, this this
this this core
technology, I say, that's actually
the the tech. The rest of the device,
you know, we talked about this the the
clinical study being involving an external pacing system
that we've modified with our technology.
So 99%
of the device is is just a standard
pacemaker and the implantable will be exactly the
same. It's just a pacemaker with our with
our chip
in place. So I think we started with
the premise that, you know, let's let's go
and talk to Medtronic or one of the
other big corporates.
They'll give us their pacemaker. We'll put our
chip in it. And there we go. That's,
that's, that's, that's kind of done. And there
were 2 things that we've learned over the
years. 1, they're not prepared to do that.
And 2, we don't need them to do
that actually because because this technology has been
around since the fifties,
most of the most of what's
required is there
is available from particular support. The technology and
the challenge of putting them together is not,
is not that great. So I think we're
much more self sufficient now than we were,
you know, 3 or 4 years ago.
When we
in terms of the route that we're choosing
to develop this technology, it's like, you know,
no one's gonna help you do this. You
just gotta do it yourself, but actually, doing
it yourself is probably the most efficient way
to do it anyway. So
Ashok, do you have anything to add to
that?
I I would add from my point of
view, I think
transition from academia to industry
has been a big learning,
although you hear lots of
suggestions,
they're all valid, but experiencing them and
actually, dealing with them is a slightly different
story. But,
especially with the start ups, things are very
dynamic.
And the key difference between academia and industry
is the pace at which you can do
the things. Of course, a lot of academic
work has been done. And when
you're making a product, even if it is
that level of complexity going into human body,
you can do things much faster than
in academia. And
so you need to be
mentally prepared for that dynamism in the startups.
And,
the other is the communication.
So
especially in our case, because there have been
multiple disciplines involved.
And
as Stuart mentioned, investors who are not from
science background or physics background, to convince them.
So you need to
speak at multiple levels,
of complexity
and
the details. Oh, and
it's a learning process. I'm still learning, and
then but I think I've come a long
way.
There's a long way to go as well.
Well, thank you both for for, coming and
and and talking to me today. I really
appreciate it. Stuart Naschach, thank you very much
for joining us in the Physicworld podcast.
Brilliant. Thank you very much.
I'm afraid that's all the time we have
for this week's podcast.
Thanks to CRX Medical's
Stuart Plant
and Ashok Chowan
for a fascinating discussion,
And also thanks to Margaret Harris for asking
the questions,
and to Fred Iles for producing the audio
in this podcast.
We'll be back again next week.