December 1, 2021 • 35 mins
Episode 48 of The Sugar Mama's Podcast features Dr. Matthew Webber, an associate professor of chemical and biomolecular engineering at the University of Notre Dame. He is currently in charge of a team that is studying, among other things, stimuli responsive glucagon.
This emergency glucagon or "smart glucagon" as I like to call it is a gel based technology that is injected into the body. It is able to sense when blood sugar levels are dropping to a dangerously low range and release glucagon in response to that. In other words, it has the ability to raise blood sugar levels automatically to treat lows in insulin dependent patients such as those living with type 1 diabetes.
Research like this is amazing to me and I can't wait for you to hear all about. When your done, if you want to know more about what Dr. Webber and his team are doing in their research lab, you can check them out on the Webber Lab website.
If you want to see the commercial mentioned in the episode that aired during a Notre Dame football game (this is how I found Dr. Webber) click HERE.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Katie (00:00):
Hey there, sugar, mamas, sugar, daddies, grandmas,
grandpas, aunts, uncles, friendsof T1, D anyone.
Who's a caregiver for a childliving with type one diabetes.
Welcome.
This is episode 48 of the sugarmamas podcast.
And today I'm talking with Dr.
Matthew Webber from theuniversity of Notre Dame.
He's going to tell us all aboutwhat he and his team are doing
(00:22):
in the field of type onediabetes research.
It's pretty awesome stuff.
Let's get started.
You're listening to the sugarmamas podcast, a show designed
for moms and caregivers of typeone diabetics here.
You'll find a community oflike-minded people who are
(00:43):
striving daily to keep theirkids safe, happy, and healthy in
the ever-changing world of typeone.
I'm your host and fellow T one Dmom, Katie Roseboro.
Before we get started.
I need you to know that nothingyou hear on the sugar mamas
podcast should be consideredmedical advice.
Please be safe, be smart, andalways consult your physician
(01:07):
before making changes to the wayyou manage type one diabetes.
Thanks.
Hey everybody.
I am here with Dr.
Matthew Webber today, and we'rejust going to jump right in.
I'm really excited talk with youtoday, but I'm going to let you
introduce yourself and tell thelisteners what your connection
to type one diabetes is.
Dr. Webber (01:26):
Yeah.
So I'm happy to be here todayand talk to you a little bit
about our research.
So.
Faculty member at the universityof Notre Dame.
I'm an associate professor ofchemical and biomolecular
engineering.
I run a research group at thatpresent consists of about 10
students that are pursuing theirPhD under my direction, as well
as seven scientists who alreadyhave PhDs and are working with
(01:47):
me for additional.
Katie (01:49):
Okay.
Dr. Webber (01:49):
research group is, is really focused on the idea of
making new materials and devicesthat can make the management of
blood glucose and diabetes alittle bit more autonomous.
And so thinking about strategiesto deliver things like insulin
and glucagon in a way that issensitive and responsive to
need, which need being the levelof blood glucose.
(02:11):
Right.
And so we're thinking about.
Strategies for better.
Long-term controllable glucoseusing insulin strategies for
preventing serious hypoglycemicepisodes with, with onboard
glucagon that could be deployedif needed in the event of a
serious hypo event.
And thinking about other waysfor doing better glucose
detection and glucose monitoringusing using materials and
(02:32):
device.
Katie (02:32):
long have you been at Notre Dame?
Dr. Webber (02:34):
But in Notre Dame almost a little over five years.
And so I started my researchgroup here the fall of 2016
Katie (02:40):
And have you been working in the type one diabetes sealed
with, in terms of your researchsince you started there?
Dr. Webber (02:46):
at Notre Dame.
Yeah.
We've been doing, we have wehave other angles of our
research as well.
We, we pursue a few other typesof things here.
But a large portion of ourresearch group, especially
reflected in the, the fundingand the awards we have are in
the diabetes space.
And so we're very interestedjust generally in stimuli,
responsive materials, materialsthat can do interesting things
when exposed to a stimulus.
(03:07):
And in the context of diabetes,that stimulus is glucose.
For other things, maybe we'rethinking about, you know, other,
other interesting diseasemarkers, or other things for
other therapies or we'redesigning, our primary focus is
in glucose response.
Katie (03:18):
In case listeners are wondering, I found Dr.
Webber through a commercial thatI saw that was aired during a
Notre Dame football game.
And in the commercial, it kindof started by interviewing
parents of a probably six orseven year old boy that has type
one diabetes and then kind oftransitioned into talking about
how Dr.
Weber and his team at Notre Dameare researching a, the
(03:42):
commercial.
Referred to it as a gel basedtechnology that can detect
dropping levels of glucose inthe blood and then release the
necessary amount of glucagon to,to stop that to safely stop
that.
So, it sounds like you're doinga lot more than just looking
into this gel based product, buttell us a little bit about,
(04:03):
about that.
Dr. Webber (04:06):
Yeah.
Glucagon project is one thatwe're kind of trying to take a
new spin on, on the delivery oftherapeutics and the glucose
responsive way.
And so I would say historicallyin the field of diet, The
glucose responsive insulin hasbeen kind of a promise for, for
the last several decades that isstill in development and maybe
(04:26):
isn't isn't fully available yet,but the idea there would be
you'd have an insulin that couldbe mobilized or have its potency
increased as glucose levels go.
And so what we've been thinkingabout instead is reverse
engineering.
A lot of those sensing andresponse mechanisms that have
been explored for glucoseresponsive insulin, and instead
designing materials where theyare in fact stabilized in the
(04:48):
presence of glucose and thendestabilize or fall apart or
degrade in the absence ofglucose or under, under low
glucose conditions.
And so that's been kind of the,the motivation for our work was
take what we know.
About glucose, responsiveinsulin things that I've worked
on, you know, for years as apostdoc and my own training and
then try to flip that and doglucose responsive glucagon.
(05:11):
And so the gel you're speakingof is kind of our first pass at
this, this technology.
We have a system that we caninject.
Under the skin, we've donestudies through mouse studies at
this point.
And so there's still a lot ofdevelopment left to be, to be
done on this particulartechnology, but it's an easily
injectable gel, very lowviscosity goes in, goes into
under the skin, and then itholds glucagon in place and sort
(05:32):
of a Depot there.
But if in the event of a, of ahypoglycemic onset, which we
stimulate by an insulin.
The gel just to solves and theglucagon that was encapsulated
comes out.
And so in our models, when we,when we do a hypoglycemic
induced event by insulinoverdose in these mice, we find
that the blood glucose levelsdon't go nearly as low when they
(05:54):
have our device on board.
They recover a lot faster,importantly, they don't die
where in the control cases, theysometimes die.
And so.
We're hopeful for thistechnology.
I think there's still somethings that we need to to try to
improve, but we've now got kindof generation one of this
technology demonstrated, whichis sort of a new concept in
this, this glucose responsivetherapeutic space hoping to
(06:17):
build on and make things thatwould be a little bit more
viable.
So there's issues with thecurrent technology that we know
about.
We're trying to engineer thoseissues out with a series of
iterative improvements andtrying to make a better
technology in the end.
Katie (06:29):
So how does that work physiologically?
what, what about this gel basedtechnology triggers it to
dissolve and release theglucagon.
I mean, you said the rising orthe dropping, excuse me, the
dropping blood sugar levels, butI'm just curious to know, like
at the cellular level, what,what triggers that.
Dr. Webber (06:47):
Yeah.
So we're using glucose sensingchemistry.
And we're using alsoenzymatically responsive
enzymatically, I guessactuatable chemistries, I could
say.
And so when you think about likehow a continuous glucose monitor
works or a handheld glucosemeter works many of these
function on the basis of anenzyme that's known as glucose,
(07:08):
oxidase and glucose oxidase canconvert glucose into.
Gluconic acid and hydrogenperoxide.
so your continuous glucosemonitor and your handheld meter
are actually reading thehydrogen peroxide product of
that glucose oxidase conversion.
And so this is known technologyfor, for being able to measure
blood glucose normally.
(07:30):
And so what we do in our firstiteration of this is we've
included glucose oxidase intoour materia.
To do the glucose sensing piece,but instead of actually
detecting the hydrogen peroxideas your CGM or as your handheld
glucose meter would do we'reactually using the gluconic acid
product to drive changes in ourmaterial.
Katie (07:47):
Wow.
Okay.
Very interesting.
So is the idea that, you know,type one diabetics would inject
this, like once a day, once aweek, is it kind of like a long
lasting insulin type of thingwhere it lasts for 24 to 48
hours?
Or what would be the kind of theclinical of it?
Dr. Webber (08:06):
Yeah, I think that's still to be determined.
I would say probably the mostlikely form factor would be, you
know, a nightly injectable, forinstance you know, something
before bed time, you have a, youknow, you have a shot of this
stuff.
You've got your glucagon onboard at the ready in the event
of some nocturnal hypoglycemicepisode, which is the one.
You know, cause parents anddiabetics, you know, the most
(08:28):
stress and anxiety and, youknow, are the most lethal.
Right?
And then you've got this sort ofat the ready in the event of
some, a subsequent event.
And so if it was that way, it'dbe kind of a nightly thing.
If the gel doesn't deploy for ahypoglycemic episode, you know,
there'd probably be some lowlevel of glucagon activity kind
of released from the materialover time, maybe over a period
(08:49):
of 12 to 24 hours.
And the material itself haspretty readily cleared.
And so ideally that would besort of just a, you know, you,
it would, it would sort ofclear, clear normally in the
event that it wasn't activelydeployed in their response to a
hypoglycemic event potentially alittle bit of glucagon activity
associated with some leakage.
Katie (09:08):
Okay.
earlier you referenced theglucose responsive insulin, is
that what I've heard?
People call smart kind of smartinsulin, like where it only.
we'll respond when blood sugarlevels get too high.
Correct.
Is that smart insulin?
Dr. Webber (09:21):
I think that's probably similar.
Yeah.
Katie (09:23):
Okay.
Okay.
And So this is, this is more oflike a smart, a smart glucagon.
So in, is it so smart that itwould actually only release the
amount to bring the glucoselevels back up to like a certain
level?
Or what have you seen in themice in terms of bringing them
back up?
You know, I'm, I'm assuming thatyou wouldn't want it to like
skyrocket the blood sugars, butwhat have you seen.
Dr. Webber (09:45):
So our initial technology is admittedly not
very smart.
And so I think I think we haveyou know, issues.
I think I mentioned, you know,we've, we've got some known
issues.
One of them is that the glucagondoes leak out a little bit on
injection.
And so we do see a little bit ofa spike initially on.
Which isn't ideal, right?
You wouldn't want to do anythingto sort of confound or disrupt
(10:06):
the insulin centered controlblood glucose.
we'd like to get that leakagedown.
And then I think we're thinking,you know, like but what we, what
we see from there is when we dothese insulin challenges, the
depth, like the well that wewould get in sort of the low
point of blood glucose followingthe insulin overdose isn't.
And then a couple hours afterinsulin challenged, they're back
(10:27):
to a normal level.
Whereas our control mice arestill maybe cruising along at a
60 or a 70 milligram perdeciliter level.
So it's still pretty low.
You know, we we're, we're inthe, you know, one 20 to one 30
range, for instance, in our, inour prophylactic treated mice
are mice that were treatedbefore the challenge with our.
Katie (10:45):
So at what point in, in a
Dr. Webber (10:47):
Yeah,
Katie (10:48):
reading, would the gel respond and release glucagon?
Like, is there a certain number,you know, could you translate it
into like a number for where itwould kick in.
Dr. Webber (10:58):
no, I think the challenge with the technology
we're using is you, you can'treally think about it like a
light switch, sort of like anon-off kind of release.
I would maybe think about itmore in the context of a dimmer
switch, where it releases more,the lower the blood glucose
goes.
And so it'll release summit 200milligrams per deciliter, or at
least more at a hundred.
It will release more at 50 it'llrelease more at 25 it'll release
(11:21):
more at zero.
And so there's sort of, it'ssort of, it's kind of increasing
the release rate as bloodglucose goes down.
And so it's not like it wouldjust kind of click on.
I think that would be reallynice.
It may not be possible in thecontext of sort of the kinds of
materials we're designing thathave sort of that very sudden
rapid event.
Katie (11:38):
Yeah.
Dr. Webber (11:38):
about other ways of having a more sudden and rapid
event which we haven't wehaven't disclosed really in that
kind of stuff yet, but I thinkfor now, what we're working
with, you could think of as likea dimmer switch, right?
No more or less releaseddepending on what glucose level.
It'd be great to get
Katie (11:53):
Okay.
Dr. Webber (11:54):
no release until, you know, you're at 55
milligrams per deciliter orsomething looking pretty
dangerously low.
And then thing flips on and getsyou back up to one 20.
I think that'd be really great.
I think the engineering of thatis considerably more complex
from a injectable.
Um, maybe, you know, certainlyby hormonal pump or something
like that might be able toachieve that kind of bolus
(12:16):
administration upon hitting thatlevel.
are not, we're not able to dothat with our, our formulation
approach.
Katie (12:21):
Well, I mean, earlier you mentioned the whole not dying
thing, which is it's a majorbonus, right?
I mean, let's be honest.
That's kind of a.
Biggest fear with having a typeone diabetic child is that their
blood sugar is going to get solow.
That something really, reallyhorrible and serious is going to
happen.
So, you know, ultimately to me,at least if they were having
like a really severehypoglycemic event in the middle
(12:44):
of the night, I wouldn't carewhat number, any technology
brought their number back up to.
As long as it's within a, youknow, a range, that's not going
to send them into.
Into a coma.
But, and, and like you said,there's, you know, if it, if, if
blood sugars do get too high,whether that's from, you know,
nasal spray, glucagon, orinjectable glucagon, or this gel
based technology, then we have,have things to treat that too.
(13:06):
Right.
We can, we can bring it backdown with insulin.
So in my mind, at the moment,ultimately, it just, it doesn't
matter.
I just think it's amazing thatyou guys are working on
developing this technology tohave a smart glucagon It just
would give us a lot of peace ofmind to know that there's a
backup system, right?
I mean, our liver itself is abackup system, but in the, in
these circumstances where you'veoverdosed on insulin, it can
(13:28):
only do so much.
Right.
So it would be nice to knowthere's a, a backup to the
backup system.
Dr. Webber (13:33):
Yeah, and I think that's that's key.
And I also think, you know,Increasingly it's appreciated
that.
I think maybe an ignored aspectof, of type one diabetes and
understanding the diseases thatyou know, we all know the beta
cell, you know, is, is, is gone.
And the, in the case of type onediabetes doesn't produce the
insulin or the amylin.
But the alpha cells also forwhatever reason are pretty, are
(13:53):
a little bit dysregulated, theones that secrete glucagon.
And so even sometimes those,those stores in the liver kind
of that emergency backup.
Aren't aren't properly utilizedeven even in type one diabetes
because glucagon signaling forwhatever reason is also a little
bit dysregulated or kind of theresponsiveness is, is
dysregulated.
And so I think that's actuallyvery, and I'm not a biologist,
(14:15):
but I think there's someinteresting biology.
That's, that's kind of startingto uncover some of the
mechanisms of this alpha celldysregulation and type one
diabetes that is probably awhole other, you know, a way to
understand how to treat.
to control blood glucose.
And so I'm kind of curious tosee where that research leads as
well.
Katie (14:33):
Yeah, so this is in the development phase with the gel
based technology, the smartglucagon, or
Dr. Webber (14:38):
very early development.
Katie (14:40):
early.
Okay.
Dr. Webber (14:41):
And so whenever I, whenever I do these podcasts,
I'm always, you know, I'm alwayshesitant to oversell.
You know, I've done a few ofthese now and I would just, you
know, I say, you know, we'reworking on better technologies
or we're trying, I think there'sa, there's a hopeful future for
better methods of blood glucosecontrol in the future.
We're not there yet.
And so we're really, you know,we're, we're trying to get stuff
that we would feel good about.
(15:02):
You know, bringing to that nextlevel, bringing into clinical
use actually treating.
And and, and we're not, we'renot quite there yet.
And so I always, I always feelbad when I do these things.
I don't want to give peoplefalse hope or, you know,
sometimes people don't alwaysappreciate the, the runway to
development of a new product ora new technology and getting
that into.
Into human use and kind of thestage of where we are.
(15:23):
And so kind of by way of fulldisclosure, you know, we're,
we're working, we're trying tomake progress, but we're not
we're not actively enrolling inclinical trials yet.
For instance, we are, we'restill trying to get the system
to work and work better.
And so I do I do like to sort offrame this in that context.
Katie (15:38):
Absolutely.
No, I, these things obviouslytake a whole lot of time to
develop and test and, and makesure they're safe and, and
things like that.
But what, so what would be nextsteps for, for this particular
product?
Dr. Webber (15:51):
You know, I think like, I think as I mentioned,
our first demonstration, I don'tthink is clinically viable for a
few reasons.
And so we're going back andwe're, re-engineering a lot of
that.
And so from an academicperspective, we wanted to
demonstrate this concept for thefield that hadn't been
demonstrated before.
Now that we've done that, we'rekind of thinking about, you
know, okay, now can we make thisbetter?
How can we prevent some of thisearly leakage?
(16:13):
How can we make the responsefaster?
All right.
Do you know, how can we make theresponse, you know, more
appropriately tuned for, for thedesired end point like glucose
that may be.
Following a hypo event.
And so I think these are allconsiderations that we're going
to, we're continuing to, to totake into the design of the
system and tweaking different,different parameters and trying
(16:33):
to make things better.
We're starting to play withdifferent ways of doing the
detection of, of glucose which Ithink would be, would be key to
driving, pulling costs of anysort of technology down.
And then also just simplifyingthe end product and things like
that.
Or or we're always kind ofworking to re-engineer and, and
and improve the system wherewe've kind of initially
(16:53):
demonstrated.
Katie (16:54):
Yeah.
Well, you've mentioned a fewother areas that you're working
on also in the realm of type onediabetes.
Would you mind telling us alittle bit about those also?
We're taking a super quick breakfrom my interview with Dr.
Matthew Weber.
So I can tell you guys about theproduct of the week.
I don't know about where youlive, but where I live right
now, it's next to impossible tofind juice boxes, especially the
(17:17):
tiny ones that we like to use.
You know, the little apple andEve brand ones with Sesame
street characters on them.
I love those because they'reonly four ounces of liquor.
But they have around 13 to 15grams of carbs.
So I feel like it's good if youneed the carbs to treat a low,
but you're also really full,like maybe my daughter to say to
meal and she can't physicallyfit more stuff in her body.
(17:40):
That's why I like to use thetiny four ounce ones.
Well, I can't find themanywhere.
So I remembered the other daythat we have these reusable
plastic four ounce bottles thatI got off of Amazon, like a year
ago when my daughter was takingGatorade.
I didn't want to send her with awhole Gatorade because I didn't
want her to drink the wholeGatorade.
You know, when she wasn'tsupposed to, I remembered I had
them.
I dug them out.
(18:01):
I've been filling them up withfour ounces of apple juice, same
brand, apple, and Eve applejuice, but the kind that comes
in the jug instead of the littlejuice boxes and it works great.
Plus it's probably better forthe environment, right.
Creates less trash and it'scheaper.
I will put the Amazon affiliatelink in the show notes so you
can check them out for yourselfand maybe consider using them.
If you haven't been over to thesugar mamas podcast, buy me a
(18:23):
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(18:46):
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Thank you so much for yoursupport.
It means the world to me, let'sget back to the show.
Dr. Webber (19:02):
Yeah.
So we have, I guess, kind of abroad glucose responsive
material interest in my group, Ithink, as I mentioned in, so
we're thinking about.
No, I think you called it smartinsulin, you know, injectable
insulins that have glucosetuneable potency or glucose
tuneable availability.
Right.
So you could imagine.
That's something where myinsulin is in a Depot and is
(19:23):
sort of sequestered there untilit's needed.
And then it is released fromthat Depot.
And can we do something likethat where you could meet sort
of the, the long, long lastingneeds that you would get from
your long acting insulin, aswell as your prandial needs that
you get from starting your fastinsulin?
Could we do that all with onesource?
System right where you'd have asingle injectable that met both
(19:43):
your basal and your prandialneeds kind of in a single shot.
And so that's one of our goals.
And then kind of building onthat.
Can we do something a little bitmore biomimetic with insulin
formulation?
And so I think one of the keythings that is that is probably
not considered enough in a.
Efforts to control blood glucoseis the role of amylin and blood
(20:08):
glucose control.
And so, you know, I mentionedthe beta cell when it is
destroyed by the immune systemto, to, to lead, to type one
diabetes onset the beta cellproduces insulin and amylin, and
both are secure.
In response to a high glucosestate that they work together
to, to lower blood glucose.
But amylin does some interestingthings with suppressing appetite
(20:29):
and with reducing postprandialhypoglycemia and with modulating
glucose absorption in the, inthe gastrointestinal system.
And yet when we treat diabeticsfor the most part, we don't, we
don't replace that animal insignal.
We do it with insulin onlyinjecting.
Or pumps or whatever it mightbe.
And so one of the areas ofinterest for our group, as well
(20:51):
as co formulating insulin andamylin AML, and the, the, the
pharmaceutical version of amylinis known as pramlintide.
And so a lot of, I, you know,the stats, I don't know the
exact numbers, but the stuffI've seen in different places or
in some of the meetings I'vebeen to what suggests that only
a few percent.
Of type one diabetics that couldbe doing, taking co formulations
(21:12):
of insulin and pramlintide oractively doing that, our co
delivery, I should say.
And part of the issue is youcan't get them in the same
injector, cause they're kind of,they're incompatible under the
same solution conditions.
And part of the issue is cost.
And part of the issue is justsort of maybe, you know, not not
pervasive enough use and thesekinds of things.
But I think that there'sprobably something to be gained.
(21:33):
Better glucose control byproviding a more biomimetic
therapeutic replacement thanjust the insulin only.
We need the insulin for sure.
The insulin is the key piecewithout insulin.
We can't control like.
But the amylin does something.
It helps.
It helps control blood glucoseas well.
And we, we, I think at present,ignore that.
And so we're thinking about waysof getting those in the same
(21:54):
vial of getting those in thesame Depot so that they can do
their work together the way theydo in a sort of a normal,
healthy functioning pancreas.
Katie (22:05):
Yeah, I am amylin slows down digestion.
Doesn't it slows down theabsorption of glucose.
Is that right?
Dr. Webber (22:11):
Yeah, it it does some interesting things with the
gastrointestinal system.
Like I said, it also is known toprevent some of these
post-prandial hypoglycemicevents that you can see you
know, when, when dosed.
And so I think there's someadded benefit.
I mean, it's you know, you needthe insulin instance key, you
know, and, know, get it, you,can you get some, know, some
Delta, some increase in, inperformance from adding this.
(22:34):
You know, how do you get peopleto, to use that?
And potentially it's not a, aviable approach for a lot of
people who are doing like a peninjector of insulin to then have
to, you know, do their insulinand do their You know, now
they've gone from, you know,four or five shots a day to
eight, 10 shots a day, whateverit is, right.
If you have to do two shotsevery time maybe that's.
(22:56):
You know, and only one of thoseis key to keeping you alive.
The other one just improvesfunction.
And so I think that there'spotentially some challenges
there to implementation, whichwe're trying to, to knock down
some of those barriers.
Katie (23:07):
Yeah, I looked into pramlintide.
I didn't realize that was theprescription name of it, but
for, for my daughter, who's onlynine.
She has type one.
She's the one with type onediabetes.
And in, I think it's only 16 andover, or maybe 18 and over, it's
only approved for older.
Kids or young adults.
So that was not an option for usat the time.
And I I've heard, I don't knowbut I've heard that some of the
(23:28):
side effects can be rough.
Dr. Webber (23:29):
Yeah, I know not nausea can be kind of bad with
it in some cases.
The dosing of it is a littletricky and it's probably a
little bit more persondependent.
I think like the exact ratiothat is released from the beta
cell and I in a healthy statebetween insulin and amylin.
Amylin is a little bit.
Varies a little bit from personto person.
And so I'm trying to match thattherapeutically as can also adds
(23:52):
a whole other challenge.
I think that, you know, I thinkpeople are still working to
address so that there's somecompanies out there that are
working on these stable amylin,variants, stable variants that
potentially could start to beput into a co-formulation with
insulin, et cetera.
So.
Katie (24:06):
Yeah, I think that's something for parents which are,
you know, the majority of mylisteners, caregivers of type
one diabetics to remember.
You know, the beta cells thatget destroyed in the onset of
type one diabetes, they do, theydo so much more than just
produce insulin.
Which is why being a pancreas isso incredibly difficult because
there's so many factors that,that to consider and that go on
(24:29):
inside the body.
You know, it's not just theinsulin production that gets
destroyed.
It's other things too, thataffect how your blood sugars up
and go down.
And all those things are, areeither of those, the the glucose
responsive insulin.
And then the, the con ofcombination of the insulin
amylin are either of those beingstudied in, in animals yet.
Dr. Webber (24:52):
Yeah, so both of those, we have, you know, we
were running animal studiesyesterday.
Actually we have some going ontoday, even with some of our
glucose responsive insulinstrategies.
We've demonstrated ways of doingbetter glucose sensing with
these materials and moreaccurate glucose response.
We've got now some strategieswhere we think we can get, you
know, 24 hour control that meetboth the basal and prandial
(25:14):
needs.
Or we can, you know, we cansimulate three meals and mice
and the, you know, the bloodglucose is corrected with each
meal with, from a single dosethat was, you know, hours prior.
And so we have some early saveson that and then the insulin
pramlintide this is something wepublished on.
I know if my good friend Ericapple out at Stanford, we worked
on this together and wepublished this.
2020.
(25:34):
We took studies of that all theway through diabetic pigs.
And so we have large animaldata.
They're demonstratingco-formulation of insulin and
pramlintide in a single vialand, and, and improved control
in diabetic pigs compared toinsulin only compared to
separate injections of insulinand pramlintide, which was a
little bit surprising to us, butit actually giving them in one
shot actually worked better thangiving two shots right next to.
(25:55):
And so there's a, there's someinteresting, I guess,
pharmacokinetic reasons for thatwe think, but yeah, this has
been, you know, some stuff we'vebeen working on for a few years
now, so.
Katie (26:04):
Hmm.
so.
I'm just curious, like the, theone you're just speaking of
where you were testing it andwhere You got it to the point
where it was being tested inpigs.
Like at what point do peoplesay, okay, now let's try to test
this in, in humans.
I'm sure it takes years andyears, but at what point do you
say let's give this a go and ina clinical trial.
Dr. Webber (26:21):
You know, there's, there's a lot of steps, I think
rightly so between where we areand where we would need to go
there.
You know, we would need to makematerials in a, in a way that
would be, you know, clean andsterile and fully validated and
all of the synthesis and thecharacterization and all of
those things.
And that's, you know, that'stypically an outside research
kind of contract organizationthat would take care of that.
(26:44):
That's not the kind of thing wewould do in an academic lab.
I don't have know clean roomsand students in bunny suits and
kind of the sterile environmentsand those kinds of things to
make the stuff that way.
And so, you know, if we've got atechnology that we wanted to get
to work, we would need to go outand typically raise some capital
to do the first stages of scaleup and manufacturing under the
(27:06):
sort of sterile and fullyregulated and validated
conditions.
From there.
Then we would take that fillingthat's, you know, kind of fully
validated material, fully doubt,validated formulation, whatever
it might be.
we would take that and we woulddo a redo safety and toxicology
studies in and typically largeanimals.
Katie (27:24):
Yeah.
Dr. Webber (27:25):
And maybe, maybe just validate, you know,
quickly, the, the efficacy wesaw in early in early studies
was, maintained using this newlysourced batch of material.
And then once you've got thatbatch that you verified safety
and toxicology, and you know,it's been made in a very clean
way.
And these kinds of things, youcould start to do a very small.
Clinical trial, I think it wouldbe the typical goal and each
(27:46):
step of the way is getting moreand more capital intensive.
And so typically it helps to tolaunch either, you know, startup
companies or partner with, withlarge.
Large pharma companies or othersorts of people who work with
venture capitalists, et cetera,to, to to raise the capital
necessary, to get over each ofthose hurdles.
And then you know, and so that'sthat period that I just
(28:09):
mentioned to go from sort of myvibe at Notre Dame to, to early
stage studies in the first fewpeople could be on the order of
a few years.
If everything goes well and itcould get derailed at any point
along the process, right?
We find out that the toxicologyisn't acceptable or, you know,
we're due.
We find out we have some, youknow, undesired, you know,
(28:30):
toxicity arising in the liverand the kidneys or the blood
work comes back and, you know,blood cells look off or things
like that.
And then this starts to kind ofderail things pretty quickly.
But assuming you get over eachof those hurdles now, you know,
maybe you're a few years to getto.
With all of these technologies.
And then that's like your firststep in people, right.
You're doing a very small stagething.
(28:50):
And then maybe you would do alarger trial and you'd study for
efficacy and you'd have, youknow, understanding of dosing
and timing of dosing and bestpractices there.
And then, and then you'd get to,you know, demonstrating how well
it works against the standard ofcare.
Right.
Sort of the, what is the currentgold standard and how well do we
work compared to that?
(29:10):
And so, you know, each of theseprocesses, as yours says, you
get down.
The path further and furthertowards clinical use the costs
go up quite a bit with eachstep.
And so so it's, it's timeintensive and capital intensive
for sure.
Katie (29:25):
I think it's good for people to hear that though.
Cause they, you know, we justdon't realize these things just
take so much time and so muchmoney and I know you guys are
working hard to.
To get things, tested and, youknow guess verified as quickly
as possible, but I think it'sgood for people to remember.
You know, we live in such an ageof, we want things and we want
things right now.
So in, in the way of at leastdiabetes research, you know,
(29:47):
it's, it's happening and it'sgood, but it, it just takes such
a long time, which you obviouslyare very well aware.
Dr. Webber (29:54):
and I'm aware, and I appreciate the, the impatience
of especially parents.
You know, who want to see bettertechnologies for their children,
who they, they don't want to seesuffering.
They want to see have normallives and be able to, you know,
to do the things that, you know,other kids do without having to
worry without the anxiety,without the constant decision
(30:16):
making and monitoring and thesekinds of things.
And so, I mean, that's thereason we try to develop the
technologies we develop.
And I fully understand thatpeople are impatient and they
want these things yesterday.
Right.
And, and and that's, that'sgreat.
And I think.
You know, I think, especially ina parents of diabetic children
and especially the mothers ofdiabetic children are just a
force of nature and they're justthe most inspiring people.
(30:36):
And how, when you think aboutit, you know, they call my
office, they come see me.
They, you know, they, they emailme constantly, you know, wanting
to know more about when thesetechnologies are going to be
available.
When are we going to be able tohelp, you know, children and,
you know, and I think, you know,they've done some of the
greatest greatest work for, fortype one diabetes, you know, In
history, which is, you know, Imean the, you know, the two
(30:58):
mothers who, who are thefounders of JDRF, right?
And like JDRF is a phenomenalorganization that has done so
much good for improving standardof care for, for diabetics.
And so, you know, like I said,I, I appreciate how passionate
are.
I, I appreciate how impatientthey are and certainly that
motive that motivates, and thatfuels our, our work as well.
Katie (31:21):
Yeah, I don't think I've ever heard anybody say thank you
for being so impatient.
I like that.
Dr. Webber (31:27):
Well, I mean, I it's awesome.
It's great.
I think, you know, I mean, Ithink this is what drives us,
right?
We know that there's a need outthere that people want, and that
fuels us to try to deliver thosenew technologies and those new
solutions, right.
For a problem that clearlyexists and clearly has a, has a,
a, you know, a large cohort ofpeople that are, that are super
passionate about seeing this.
Katie (31:49):
absolutely.
We want the best for our kids.
So thank you so much for thework that you're doing in your
lab at Notre Dame.
And thank you for again, takingthe time to come on and talk to
me today.
I will leave a link in the shownotes to where people can find
out more about the researchwe're doing and kind of follow
along as you guys progress.
Dr. Webber (32:05):
Yeah, I appreciate that.
It's, you know, it's fantastic.
Come here and talk with you.
And I never turned down a chanceto talk about our work because
of.
Because of how much I know thatthis, you know, the stuff we're
doing means to people and also,you know, talking with you and
we know, and meeting yourlisteners and other sorts of
people really helps inspire thework we do.
And I get to go back and tellthe team about the people I meet
(32:25):
and the stories I hear and youknow, how the things they're
doing are, you know, beyond justthem in their thesis research or
the next paper, they want towrite that.
We're really thinking about howwe can bring something to
fruition that.
That could really have an impactin people's lives.
And so I think that really addsmeaning and adds value to the
things we do for sure.
And so I, I love having thesekinds of conversations, so I
(32:45):
appreciate the opportunity totake it, to talk about what we
do.
Katie (32:49):
Yeah, I'm just curious.
Does anybody on your team havetype one diabetes?
Dr. Webber (32:52):
Yeah.
I have one person on my team andI was type one diabetes.
And you'd believe.
He's one of my only ones thatdoesn't work on a diabetes
relevant research project.
Katie (33:00):
Yeah.
Dr. Webber (33:01):
I, I gave, I gave him the option and he basically,
you know, when he started and hesaid, you know, that's kind of
like everyday life for me.
And if you don't mind, I'dprefer to do something that
wasn't, it wasn't so personal.
And I said, yeah, then that'sperfectly fine.
And so so he's got a greatproject on.
You know, materials that couldthat could be triggered in the
presence of localizedinflammation in the body and
(33:22):
deliver drugs to localized areasof inflammation, which may be,
would have a role in, you know,autoimmune types of diseases
like diabetes, but maybe, youknow, other things as well.
Katie (33:32):
what did you call it earlier?
The it's the response likeyou're all of the things you're
working on in your lab, typeone, diabetes, diabetes related
or not, they all have to do withsensor responses.
What did you call it?
Dr. Webber (33:44):
Yeah, like stimuli, responsive materials is really
sort of our interest.
And so I'm, I'm bored by thingsthat don't move.
I'm bored by things that juststay static.
And so I really like things thatcan undergo interesting changes
as, or as a result of somestimulus.
And so these are, are materialsthat have always just kind of
excited me.
How can we engineer things thatcan, that can have a
(34:04):
communication with the livingworld can talk to things like
blood glucose or to cytokines orto you know pH or other sorts of
triggers that are relevant fordifferent diseases.
And how can we use those to thendrive changes in materials in a
way that would be responsive tothose needs?
Katie (34:21):
Amazing.
You guys are brilliant.
I love it.
thank you again, Dr.
Webber, and I'll be definitelybe keeping up with you.
I'm interested to see where thisgoes.
Dr. Webber (34:28):
No.
Thank you very much, Katie, forthe chance to talk to you, it's
been great to about our work, soI appreciate it
Katie (34:34):
Yeah, you're very welcome.
You have a nice week.
Dr. Webber (34:36):
And DTS you as well.
Katie (34:38):
Thank you.
And that's a wrap.
You guys know what to do head onover to the show notes and look
for all the links.
I'll put a link to where you canlearn more about what Dr.
Weber in his team is doing overat Notre Dame.
I'll put a link to the productfeature of the week, those
little four ounce plastic juicebottles, a link to buy me a
coffee, if you want to supportthe show so I can keep bringing
(35:01):
awesome content to you each andevery week, and probably a link
to something else.
Just check it out.
It'll be a surprise when you getthere.
I hope you guys had a greatThanksgiving.
Thanksgiving was last week and Ireally hope you took the time to
listen to diabetes, the musical.
I hope that put a little pep inyour step, this holiday season,
and I hope you are going to besinging your way through the new
year.
All right guys, have a fabulousweek and I'll talk with you
(35:22):
soon.
Bye.
Hey there, sugar, mamas, sugar, daddies, grandmas,
grandpas, aunts, uncles, friendsof T1, D anyone.
Who's a caregiver for a childliving with type one diabetes.
Welcome.
This is episode 48 of the sugarmamas podcast.
And today I'm talking with Dr.
Matthew Webber from theuniversity of Notre Dame.
He's going to tell us all aboutwhat he and his team are doing
(00:22):
in the field of type onediabetes research.
It's pretty awesome stuff.
Let's get started.
You're listening to the sugarmamas podcast, a show designed
for moms and caregivers of typeone diabetics here.
You'll find a community oflike-minded people who are
(00:43):
striving daily to keep theirkids safe, happy, and healthy in
the ever-changing world of typeone.
I'm your host and fellow T one Dmom, Katie Roseboro.
Before we get started.
I need you to know that nothingyou hear on the sugar mamas
podcast should be consideredmedical advice.
Please be safe, be smart, andalways consult your physician
(01:07):
before making changes to the wayyou manage type one diabetes.
Thanks.
Hey everybody.
I am here with Dr.
Matthew Webber today, and we'rejust going to jump right in.
I'm really excited talk with youtoday, but I'm going to let you
introduce yourself and tell thelisteners what your connection
to type one diabetes is.
Dr. Webber (01:26):
Yeah.
So I'm happy to be here todayand talk to you a little bit
about our research.
So.
Faculty member at the universityof Notre Dame.
I'm an associate professor ofchemical and biomolecular
engineering.
I run a research group at thatpresent consists of about 10
students that are pursuing theirPhD under my direction, as well
as seven scientists who alreadyhave PhDs and are working with
(01:47):
me for additional.
Katie (01:49):
Okay.
Dr. Webber (01:49):
research group is, is really focused on the idea of
making new materials and devicesthat can make the management of
blood glucose and diabetes alittle bit more autonomous.
And so thinking about strategiesto deliver things like insulin
and glucagon in a way that issensitive and responsive to
need, which need being the levelof blood glucose.
(02:11):
Right.
And so we're thinking about.
Strategies for better.
Long-term controllable glucoseusing insulin strategies for
preventing serious hypoglycemicepisodes with, with onboard
glucagon that could be deployedif needed in the event of a
serious hypo event.
And thinking about other waysfor doing better glucose
detection and glucose monitoringusing using materials and
(02:32):
device.
Katie (02:32):
long have you been at Notre Dame?
Dr. Webber (02:34):
But in Notre Dame almost a little over five years.
And so I started my researchgroup here the fall of 2016
Katie (02:40):
And have you been working in the type one diabetes sealed
with, in terms of your researchsince you started there?
Dr. Webber (02:46):
at Notre Dame.
Yeah.
We've been doing, we have wehave other angles of our
research as well.
We, we pursue a few other typesof things here.
But a large portion of ourresearch group, especially
reflected in the, the fundingand the awards we have are in
the diabetes space.
And so we're very interestedjust generally in stimuli,
responsive materials, materialsthat can do interesting things
when exposed to a stimulus.
(03:07):
And in the context of diabetes,that stimulus is glucose.
For other things, maybe we'rethinking about, you know, other,
other interesting diseasemarkers, or other things for
other therapies or we'redesigning, our primary focus is
in glucose response.
Katie (03:18):
In case listeners are wondering, I found Dr.
Webber through a commercial thatI saw that was aired during a
Notre Dame football game.
And in the commercial, it kindof started by interviewing
parents of a probably six orseven year old boy that has type
one diabetes and then kind oftransitioned into talking about
how Dr.
Weber and his team at Notre Dameare researching a, the
(03:42):
commercial.
Referred to it as a gel basedtechnology that can detect
dropping levels of glucose inthe blood and then release the
necessary amount of glucagon to,to stop that to safely stop
that.
So, it sounds like you're doinga lot more than just looking
into this gel based product, buttell us a little bit about,
(04:03):
about that.
Dr. Webber (04:06):
Yeah.
Glucagon project is one thatwe're kind of trying to take a
new spin on, on the delivery oftherapeutics and the glucose
responsive way.
And so I would say historicallyin the field of diet, The
glucose responsive insulin hasbeen kind of a promise for, for
the last several decades that isstill in development and maybe
(04:26):
isn't isn't fully available yet,but the idea there would be
you'd have an insulin that couldbe mobilized or have its potency
increased as glucose levels go.
And so what we've been thinkingabout instead is reverse
engineering.
A lot of those sensing andresponse mechanisms that have
been explored for glucoseresponsive insulin, and instead
designing materials where theyare in fact stabilized in the
(04:48):
presence of glucose and thendestabilize or fall apart or
degrade in the absence ofglucose or under, under low
glucose conditions.
And so that's been kind of the,the motivation for our work was
take what we know.
About glucose, responsiveinsulin things that I've worked
on, you know, for years as apostdoc and my own training and
then try to flip that and doglucose responsive glucagon.
(05:11):
And so the gel you're speakingof is kind of our first pass at
this, this technology.
We have a system that we caninject.
Under the skin, we've donestudies through mouse studies at
this point.
And so there's still a lot ofdevelopment left to be, to be
done on this particulartechnology, but it's an easily
injectable gel, very lowviscosity goes in, goes into
under the skin, and then itholds glucagon in place and sort
(05:32):
of a Depot there.
But if in the event of a, of ahypoglycemic onset, which we
stimulate by an insulin.
The gel just to solves and theglucagon that was encapsulated
comes out.
And so in our models, when we,when we do a hypoglycemic
induced event by insulinoverdose in these mice, we find
that the blood glucose levelsdon't go nearly as low when they
(05:54):
have our device on board.
They recover a lot faster,importantly, they don't die
where in the control cases, theysometimes die.
And so.
We're hopeful for thistechnology.
I think there's still somethings that we need to to try to
improve, but we've now got kindof generation one of this
technology demonstrated, whichis sort of a new concept in
this, this glucose responsivetherapeutic space hoping to
(06:17):
build on and make things thatwould be a little bit more
viable.
So there's issues with thecurrent technology that we know
about.
We're trying to engineer thoseissues out with a series of
iterative improvements andtrying to make a better
technology in the end.
Katie (06:29):
So how does that work physiologically?
what, what about this gel basedtechnology triggers it to
dissolve and release theglucagon.
I mean, you said the rising orthe dropping, excuse me, the
dropping blood sugar levels, butI'm just curious to know, like
at the cellular level, what,what triggers that.
Dr. Webber (06:47):
Yeah.
So we're using glucose sensingchemistry.
And we're using alsoenzymatically responsive
enzymatically, I guessactuatable chemistries, I could
say.
And so when you think about likehow a continuous glucose monitor
works or a handheld glucosemeter works many of these
function on the basis of anenzyme that's known as glucose,
(07:08):
oxidase and glucose oxidase canconvert glucose into.
Gluconic acid and hydrogenperoxide.
so your continuous glucosemonitor and your handheld meter
are actually reading thehydrogen peroxide product of
that glucose oxidase conversion.
And so this is known technologyfor, for being able to measure
blood glucose normally.
(07:30):
And so what we do in our firstiteration of this is we've
included glucose oxidase intoour materia.
To do the glucose sensing piece,but instead of actually
detecting the hydrogen peroxideas your CGM or as your handheld
glucose meter would do we'reactually using the gluconic acid
product to drive changes in ourmaterial.
Katie (07:47):
Wow.
Okay.
Very interesting.
So is the idea that, you know,type one diabetics would inject
this, like once a day, once aweek, is it kind of like a long
lasting insulin type of thingwhere it lasts for 24 to 48
hours?
Or what would be the kind of theclinical of it?
Dr. Webber (08:06):
Yeah, I think that's still to be determined.
I would say probably the mostlikely form factor would be, you
know, a nightly injectable, forinstance you know, something
before bed time, you have a, youknow, you have a shot of this
stuff.
You've got your glucagon onboard at the ready in the event
of some nocturnal hypoglycemicepisode, which is the one.
You know, cause parents anddiabetics, you know, the most
(08:28):
stress and anxiety and, youknow, are the most lethal.
Right?
And then you've got this sort ofat the ready in the event of
some, a subsequent event.
And so if it was that way, it'dbe kind of a nightly thing.
If the gel doesn't deploy for ahypoglycemic episode, you know,
there'd probably be some lowlevel of glucagon activity kind
of released from the materialover time, maybe over a period
(08:49):
of 12 to 24 hours.
And the material itself haspretty readily cleared.
And so ideally that would besort of just a, you know, you,
it would, it would sort ofclear, clear normally in the
event that it wasn't activelydeployed in their response to a
hypoglycemic event potentially alittle bit of glucagon activity
associated with some leakage.
Katie (09:08):
Okay.
earlier you referenced theglucose responsive insulin, is
that what I've heard?
People call smart kind of smartinsulin, like where it only.
we'll respond when blood sugarlevels get too high.
Correct.
Is that smart insulin?
Dr. Webber (09:21):
I think that's probably similar.
Yeah.
Katie (09:23):
Okay.
Okay.
And So this is, this is more oflike a smart, a smart glucagon.
So in, is it so smart that itwould actually only release the
amount to bring the glucoselevels back up to like a certain
level?
Or what have you seen in themice in terms of bringing them
back up?
You know, I'm, I'm assuming thatyou wouldn't want it to like
skyrocket the blood sugars, butwhat have you seen.
Dr. Webber (09:45):
So our initial technology is admittedly not
very smart.
And so I think I think we haveyou know, issues.
I think I mentioned, you know,we've, we've got some known
issues.
One of them is that the glucagondoes leak out a little bit on
injection.
And so we do see a little bit ofa spike initially on.
Which isn't ideal, right?
You wouldn't want to do anythingto sort of confound or disrupt
(10:06):
the insulin centered controlblood glucose.
we'd like to get that leakagedown.
And then I think we're thinking,you know, like but what we, what
we see from there is when we dothese insulin challenges, the
depth, like the well that wewould get in sort of the low
point of blood glucose followingthe insulin overdose isn't.
And then a couple hours afterinsulin challenged, they're back
(10:27):
to a normal level.
Whereas our control mice arestill maybe cruising along at a
60 or a 70 milligram perdeciliter level.
So it's still pretty low.
You know, we we're, we're inthe, you know, one 20 to one 30
range, for instance, in our, inour prophylactic treated mice
are mice that were treatedbefore the challenge with our.
Katie (10:45):
So at what point in, in a
Dr. Webber (10:47):
Yeah,
Katie (10:48):
reading, would the gel respond and release glucagon?
Like, is there a certain number,you know, could you translate it
into like a number for where itwould kick in.
Dr. Webber (10:58):
no, I think the challenge with the technology
we're using is you, you can'treally think about it like a
light switch, sort of like anon-off kind of release.
I would maybe think about itmore in the context of a dimmer
switch, where it releases more,the lower the blood glucose
goes.
And so it'll release summit 200milligrams per deciliter, or at
least more at a hundred.
It will release more at 50 it'llrelease more at 25 it'll release
(11:21):
more at zero.
And so there's sort of, it'ssort of, it's kind of increasing
the release rate as bloodglucose goes down.
And so it's not like it wouldjust kind of click on.
I think that would be reallynice.
It may not be possible in thecontext of sort of the kinds of
materials we're designing thathave sort of that very sudden
rapid event.
Katie (11:38):
Yeah.
Dr. Webber (11:38):
about other ways of having a more sudden and rapid
event which we haven't wehaven't disclosed really in that
kind of stuff yet, but I thinkfor now, what we're working
with, you could think of as likea dimmer switch, right?
No more or less releaseddepending on what glucose level.
It'd be great to get
Katie (11:53):
Okay.
Dr. Webber (11:54):
no release until, you know, you're at 55
milligrams per deciliter orsomething looking pretty
dangerously low.
And then thing flips on and getsyou back up to one 20.
I think that'd be really great.
I think the engineering of thatis considerably more complex
from a injectable.
Um, maybe, you know, certainlyby hormonal pump or something
like that might be able toachieve that kind of bolus
(12:16):
administration upon hitting thatlevel.
are not, we're not able to dothat with our, our formulation
approach.
Katie (12:21):
Well, I mean, earlier you mentioned the whole not dying
thing, which is it's a majorbonus, right?
I mean, let's be honest.
That's kind of a.
Biggest fear with having a typeone diabetic child is that their
blood sugar is going to get solow.
That something really, reallyhorrible and serious is going to
happen.
So, you know, ultimately to me,at least if they were having
like a really severehypoglycemic event in the middle
(12:44):
of the night, I wouldn't carewhat number, any technology
brought their number back up to.
As long as it's within a, youknow, a range, that's not going
to send them into.
Into a coma.
But, and, and like you said,there's, you know, if it, if, if
blood sugars do get too high,whether that's from, you know,
nasal spray, glucagon, orinjectable glucagon, or this gel
based technology, then we have,have things to treat that too.
(13:06):
Right.
We can, we can bring it backdown with insulin.
So in my mind, at the moment,ultimately, it just, it doesn't
matter.
I just think it's amazing thatyou guys are working on
developing this technology tohave a smart glucagon It just
would give us a lot of peace ofmind to know that there's a
backup system, right?
I mean, our liver itself is abackup system, but in the, in
these circumstances where you'veoverdosed on insulin, it can
(13:28):
only do so much.
Right.
So it would be nice to knowthere's a, a backup to the
backup system.
Dr. Webber (13:33):
Yeah, and I think that's that's key.
And I also think, you know,Increasingly it's appreciated
that.
I think maybe an ignored aspectof, of type one diabetes and
understanding the diseases thatyou know, we all know the beta
cell, you know, is, is, is gone.
And the, in the case of type onediabetes doesn't produce the
insulin or the amylin.
But the alpha cells also forwhatever reason are pretty, are
(13:53):
a little bit dysregulated, theones that secrete glucagon.
And so even sometimes those,those stores in the liver kind
of that emergency backup.
Aren't aren't properly utilizedeven even in type one diabetes
because glucagon signaling forwhatever reason is also a little
bit dysregulated or kind of theresponsiveness is, is
dysregulated.
And so I think that's actuallyvery, and I'm not a biologist,
(14:15):
but I think there's someinteresting biology.
That's, that's kind of startingto uncover some of the
mechanisms of this alpha celldysregulation and type one
diabetes that is probably awhole other, you know, a way to
understand how to treat.
to control blood glucose.
And so I'm kind of curious tosee where that research leads as
well.
Katie (14:33):
Yeah, so this is in the development phase with the gel
based technology, the smartglucagon, or
Dr. Webber (14:38):
very early development.
Katie (14:40):
early.
Okay.
Dr. Webber (14:41):
And so whenever I, whenever I do these podcasts,
I'm always, you know, I'm alwayshesitant to oversell.
You know, I've done a few ofthese now and I would just, you
know, I say, you know, we'reworking on better technologies
or we're trying, I think there'sa, there's a hopeful future for
better methods of blood glucosecontrol in the future.
We're not there yet.
And so we're really, you know,we're, we're trying to get stuff
that we would feel good about.
(15:02):
You know, bringing to that nextlevel, bringing into clinical
use actually treating.
And and, and we're not, we'renot quite there yet.
And so I always, I always feelbad when I do these things.
I don't want to give peoplefalse hope or, you know,
sometimes people don't alwaysappreciate the, the runway to
development of a new product ora new technology and getting
that into.
Into human use and kind of thestage of where we are.
(15:23):
And so kind of by way of fulldisclosure, you know, we're,
we're working, we're trying tomake progress, but we're not
we're not actively enrolling inclinical trials yet.
For instance, we are, we'restill trying to get the system
to work and work better.
And so I do I do like to sort offrame this in that context.
Katie (15:38):
Absolutely.
No, I, these things obviouslytake a whole lot of time to
develop and test and, and makesure they're safe and, and
things like that.
But what, so what would be nextsteps for, for this particular
product?
Dr. Webber (15:51):
You know, I think like, I think as I mentioned,
our first demonstration, I don'tthink is clinically viable for a
few reasons.
And so we're going back andwe're, re-engineering a lot of
that.
And so from an academicperspective, we wanted to
demonstrate this concept for thefield that hadn't been
demonstrated before.
Now that we've done that, we'rekind of thinking about, you
know, okay, now can we make thisbetter?
How can we prevent some of thisearly leakage?
(16:13):
How can we make the responsefaster?
All right.
Do you know, how can we make theresponse, you know, more
appropriately tuned for, for thedesired end point like glucose
that may be.
Following a hypo event.
And so I think these are allconsiderations that we're going
to, we're continuing to, to totake into the design of the
system and tweaking different,different parameters and trying
(16:33):
to make things better.
We're starting to play withdifferent ways of doing the
detection of, of glucose which Ithink would be, would be key to
driving, pulling costs of anysort of technology down.
And then also just simplifyingthe end product and things like
that.
Or or we're always kind ofworking to re-engineer and, and
and improve the system wherewe've kind of initially
(16:53):
demonstrated.
Katie (16:54):
Yeah.
Well, you've mentioned a fewother areas that you're working
on also in the realm of type onediabetes.
Would you mind telling us alittle bit about those also?
We're taking a super quick breakfrom my interview with Dr.
Matthew Weber.
So I can tell you guys about theproduct of the week.
I don't know about where youlive, but where I live right
now, it's next to impossible tofind juice boxes, especially the
(17:17):
tiny ones that we like to use.
You know, the little apple andEve brand ones with Sesame
street characters on them.
I love those because they'reonly four ounces of liquor.
But they have around 13 to 15grams of carbs.
So I feel like it's good if youneed the carbs to treat a low,
but you're also really full,like maybe my daughter to say to
meal and she can't physicallyfit more stuff in her body.
(17:40):
That's why I like to use thetiny four ounce ones.
Well, I can't find themanywhere.
So I remembered the other daythat we have these reusable
plastic four ounce bottles thatI got off of Amazon, like a year
ago when my daughter was takingGatorade.
I didn't want to send her with awhole Gatorade because I didn't
want her to drink the wholeGatorade.
You know, when she wasn'tsupposed to, I remembered I had
them.
I dug them out.
(18:01):
I've been filling them up withfour ounces of apple juice, same
brand, apple, and Eve applejuice, but the kind that comes
in the jug instead of the littlejuice boxes and it works great.
Plus it's probably better forthe environment, right.
Creates less trash and it'scheaper.
I will put the Amazon affiliatelink in the show notes so you
can check them out for yourselfand maybe consider using them.
If you haven't been over to thesugar mamas podcast, buy me a
(18:23):
coffee, Paige, go check it out.
Buy me a coffee is a way forlisteners like you to support
the show hosting and producing apodcast is so much fun, but I'm
not going to lie.
It takes a lot of work to makethis thing.
Each and every week, your giftthrough buy me a coffee can be a
one-time donation, or you cansign up for one of our fun
membership levels starting atonly$1 a month.
(18:46):
Every single cent donatedthrough, buy me a coffee.
We'll go to making this show,come to life each and every week
as always.
Thank you so much for yoursupport.
It means the world to me, let'sget back to the show.
Dr. Webber (19:02):
Yeah.
So we have, I guess, kind of abroad glucose responsive
material interest in my group, Ithink, as I mentioned in, so
we're thinking about.
No, I think you called it smartinsulin, you know, injectable
insulins that have glucosetuneable potency or glucose
tuneable availability.
Right.
So you could imagine.
That's something where myinsulin is in a Depot and is
(19:23):
sort of sequestered there untilit's needed.
And then it is released fromthat Depot.
And can we do something likethat where you could meet sort
of the, the long, long lastingneeds that you would get from
your long acting insulin, aswell as your prandial needs that
you get from starting your fastinsulin?
Could we do that all with onesource?
System right where you'd have asingle injectable that met both
(19:43):
your basal and your prandialneeds kind of in a single shot.
And so that's one of our goals.
And then kind of building onthat.
Can we do something a little bitmore biomimetic with insulin
formulation?
And so I think one of the keythings that is that is probably
not considered enough in a.
Efforts to control blood glucoseis the role of amylin and blood
(20:08):
glucose control.
And so, you know, I mentionedthe beta cell when it is
destroyed by the immune systemto, to, to lead, to type one
diabetes onset the beta cellproduces insulin and amylin, and
both are secure.
In response to a high glucosestate that they work together
to, to lower blood glucose.
But amylin does some interestingthings with suppressing appetite
(20:29):
and with reducing postprandialhypoglycemia and with modulating
glucose absorption in the, inthe gastrointestinal system.
And yet when we treat diabeticsfor the most part, we don't, we
don't replace that animal insignal.
We do it with insulin onlyinjecting.
Or pumps or whatever it mightbe.
And so one of the areas ofinterest for our group, as well
(20:51):
as co formulating insulin andamylin AML, and the, the, the
pharmaceutical version of amylinis known as pramlintide.
And so a lot of, I, you know,the stats, I don't know the
exact numbers, but the stuffI've seen in different places or
in some of the meetings I'vebeen to what suggests that only
a few percent.
Of type one diabetics that couldbe doing, taking co formulations
(21:12):
of insulin and pramlintide oractively doing that, our co
delivery, I should say.
And part of the issue is youcan't get them in the same
injector, cause they're kind of,they're incompatible under the
same solution conditions.
And part of the issue is cost.
And part of the issue is justsort of maybe, you know, not not
pervasive enough use and thesekinds of things.
But I think that there'sprobably something to be gained.
(21:33):
Better glucose control byproviding a more biomimetic
therapeutic replacement thanjust the insulin only.
We need the insulin for sure.
The insulin is the key piecewithout insulin.
We can't control like.
But the amylin does something.
It helps.
It helps control blood glucoseas well.
And we, we, I think at present,ignore that.
And so we're thinking about waysof getting those in the same
(21:54):
vial of getting those in thesame Depot so that they can do
their work together the way theydo in a sort of a normal,
healthy functioning pancreas.
Katie (22:05):
Yeah, I am amylin slows down digestion.
Doesn't it slows down theabsorption of glucose.
Is that right?
Dr. Webber (22:11):
Yeah, it it does some interesting things with the
gastrointestinal system.
Like I said, it also is known toprevent some of these
post-prandial hypoglycemicevents that you can see you
know, when, when dosed.
And so I think there's someadded benefit.
I mean, it's you know, you needthe insulin instance key, you
know, and, know, get it, you,can you get some, know, some
Delta, some increase in, inperformance from adding this.
(22:34):
You know, how do you get peopleto, to use that?
And potentially it's not a, aviable approach for a lot of
people who are doing like a peninjector of insulin to then have
to, you know, do their insulinand do their You know, now
they've gone from, you know,four or five shots a day to
eight, 10 shots a day, whateverit is, right.
If you have to do two shotsevery time maybe that's.
(22:56):
You know, and only one of thoseis key to keeping you alive.
The other one just improvesfunction.
And so I think that there'spotentially some challenges
there to implementation, whichwe're trying to, to knock down
some of those barriers.
Katie (23:07):
Yeah, I looked into pramlintide.
I didn't realize that was theprescription name of it, but
for, for my daughter, who's onlynine.
She has type one.
She's the one with type onediabetes.
And in, I think it's only 16 andover, or maybe 18 and over, it's
only approved for older.
Kids or young adults.
So that was not an option for usat the time.
And I I've heard, I don't knowbut I've heard that some of the
(23:28):
side effects can be rough.
Dr. Webber (23:29):
Yeah, I know not nausea can be kind of bad with
it in some cases.
The dosing of it is a littletricky and it's probably a
little bit more persondependent.
I think like the exact ratiothat is released from the beta
cell and I in a healthy statebetween insulin and amylin.
Amylin is a little bit.
Varies a little bit from personto person.
And so I'm trying to match thattherapeutically as can also adds
(23:52):
a whole other challenge.
I think that, you know, I thinkpeople are still working to
address so that there's somecompanies out there that are
working on these stable amylin,variants, stable variants that
potentially could start to beput into a co-formulation with
insulin, et cetera.
So.
Katie (24:06):
Yeah, I think that's something for parents which are,
you know, the majority of mylisteners, caregivers of type
one diabetics to remember.
You know, the beta cells thatget destroyed in the onset of
type one diabetes, they do, theydo so much more than just
produce insulin.
Which is why being a pancreas isso incredibly difficult because
there's so many factors that,that to consider and that go on
(24:29):
inside the body.
You know, it's not just theinsulin production that gets
destroyed.
It's other things too, thataffect how your blood sugars up
and go down.
And all those things are, areeither of those, the the glucose
responsive insulin.
And then the, the con ofcombination of the insulin
amylin are either of those beingstudied in, in animals yet.
Dr. Webber (24:52):
Yeah, so both of those, we have, you know, we
were running animal studiesyesterday.
Actually we have some going ontoday, even with some of our
glucose responsive insulinstrategies.
We've demonstrated ways of doingbetter glucose sensing with
these materials and moreaccurate glucose response.
We've got now some strategieswhere we think we can get, you
know, 24 hour control that meetboth the basal and prandial
(25:14):
needs.
Or we can, you know, we cansimulate three meals and mice
and the, you know, the bloodglucose is corrected with each
meal with, from a single dosethat was, you know, hours prior.
And so we have some early saveson that and then the insulin
pramlintide this is something wepublished on.
I know if my good friend Ericapple out at Stanford, we worked
on this together and wepublished this.
2020.
(25:34):
We took studies of that all theway through diabetic pigs.
And so we have large animaldata.
They're demonstratingco-formulation of insulin and
pramlintide in a single vialand, and, and improved control
in diabetic pigs compared toinsulin only compared to
separate injections of insulinand pramlintide, which was a
little bit surprising to us, butit actually giving them in one
shot actually worked better thangiving two shots right next to.
(25:55):
And so there's a, there's someinteresting, I guess,
pharmacokinetic reasons for thatwe think, but yeah, this has
been, you know, some stuff we'vebeen working on for a few years
now, so.
Katie (26:04):
Hmm.
so.
I'm just curious, like the, theone you're just speaking of
where you were testing it andwhere You got it to the point
where it was being tested inpigs.
Like at what point do peoplesay, okay, now let's try to test
this in, in humans.
I'm sure it takes years andyears, but at what point do you
say let's give this a go and ina clinical trial.
Dr. Webber (26:21):
You know, there's, there's a lot of steps, I think
rightly so between where we areand where we would need to go
there.
You know, we would need to makematerials in a, in a way that
would be, you know, clean andsterile and fully validated and
all of the synthesis and thecharacterization and all of
those things.
And that's, you know, that'stypically an outside research
kind of contract organizationthat would take care of that.
(26:44):
That's not the kind of thing wewould do in an academic lab.
I don't have know clean roomsand students in bunny suits and
kind of the sterile environmentsand those kinds of things to
make the stuff that way.
And so, you know, if we've got atechnology that we wanted to get
to work, we would need to go outand typically raise some capital
to do the first stages of scaleup and manufacturing under the
(27:06):
sort of sterile and fullyregulated and validated
conditions.
From there.
Then we would take that fillingthat's, you know, kind of fully
validated material, fully doubt,validated formulation, whatever
it might be.
we would take that and we woulddo a redo safety and toxicology
studies in and typically largeanimals.
Katie (27:24):
Yeah.
Dr. Webber (27:25):
And maybe, maybe just validate, you know,
quickly, the, the efficacy wesaw in early in early studies
was, maintained using this newlysourced batch of material.
And then once you've got thatbatch that you verified safety
and toxicology, and you know,it's been made in a very clean
way.
And these kinds of things, youcould start to do a very small.
Clinical trial, I think it wouldbe the typical goal and each
(27:46):
step of the way is getting moreand more capital intensive.
And so typically it helps to tolaunch either, you know, startup
companies or partner with, withlarge.
Large pharma companies or othersorts of people who work with
venture capitalists, et cetera,to, to to raise the capital
necessary, to get over each ofthose hurdles.
And then you know, and so that'sthat period that I just
(28:09):
mentioned to go from sort of myvibe at Notre Dame to, to early
stage studies in the first fewpeople could be on the order of
a few years.
If everything goes well and itcould get derailed at any point
along the process, right?
We find out that the toxicologyisn't acceptable or, you know,
we're due.
We find out we have some, youknow, undesired, you know,
(28:30):
toxicity arising in the liverand the kidneys or the blood
work comes back and, you know,blood cells look off or things
like that.
And then this starts to kind ofderail things pretty quickly.
But assuming you get over eachof those hurdles now, you know,
maybe you're a few years to getto.
With all of these technologies.
And then that's like your firststep in people, right.
You're doing a very small stagething.
(28:50):
And then maybe you would do alarger trial and you'd study for
efficacy and you'd have, youknow, understanding of dosing
and timing of dosing and bestpractices there.
And then, and then you'd get to,you know, demonstrating how well
it works against the standard ofcare.
Right.
Sort of the, what is the currentgold standard and how well do we
work compared to that?
(29:10):
And so, you know, each of theseprocesses, as yours says, you
get down.
The path further and furthertowards clinical use the costs
go up quite a bit with eachstep.
And so so it's, it's timeintensive and capital intensive
for sure.
Katie (29:25):
I think it's good for people to hear that though.
Cause they, you know, we justdon't realize these things just
take so much time and so muchmoney and I know you guys are
working hard to.
To get things, tested and, youknow guess verified as quickly
as possible, but I think it'sgood for people to remember.
You know, we live in such an ageof, we want things and we want
things right now.
So in, in the way of at leastdiabetes research, you know,
(29:47):
it's, it's happening and it'sgood, but it, it just takes such
a long time, which you obviouslyare very well aware.
Dr. Webber (29:54):
and I'm aware, and I appreciate the, the impatience
of especially parents.
You know, who want to see bettertechnologies for their children,
who they, they don't want to seesuffering.
They want to see have normallives and be able to, you know,
to do the things that, you know,other kids do without having to
worry without the anxiety,without the constant decision
(30:16):
making and monitoring and thesekinds of things.
And so, I mean, that's thereason we try to develop the
technologies we develop.
And I fully understand thatpeople are impatient and they
want these things yesterday.
Right.
And, and and that's, that'sgreat.
And I think.
You know, I think, especially ina parents of diabetic children
and especially the mothers ofdiabetic children are just a
force of nature and they're justthe most inspiring people.
(30:36):
And how, when you think aboutit, you know, they call my
office, they come see me.
They, you know, they, they emailme constantly, you know, wanting
to know more about when thesetechnologies are going to be
available.
When are we going to be able tohelp, you know, children and,
you know, and I think, you know,they've done some of the
greatest greatest work for, fortype one diabetes, you know, In
history, which is, you know, Imean the, you know, the two
(30:58):
mothers who, who are thefounders of JDRF, right?
And like JDRF is a phenomenalorganization that has done so
much good for improving standardof care for, for diabetics.
And so, you know, like I said,I, I appreciate how passionate
are.
I, I appreciate how impatientthey are and certainly that
motive that motivates, and thatfuels our, our work as well.
Katie (31:21):
Yeah, I don't think I've ever heard anybody say thank you
for being so impatient.
I like that.
Dr. Webber (31:27):
Well, I mean, I it's awesome.
It's great.
I think, you know, I mean, Ithink this is what drives us,
right?
We know that there's a need outthere that people want, and that
fuels us to try to deliver thosenew technologies and those new
solutions, right.
For a problem that clearlyexists and clearly has a, has a,
a, you know, a large cohort ofpeople that are, that are super
passionate about seeing this.
Katie (31:49):
absolutely.
We want the best for our kids.
So thank you so much for thework that you're doing in your
lab at Notre Dame.
And thank you for again, takingthe time to come on and talk to
me today.
I will leave a link in the shownotes to where people can find
out more about the researchwe're doing and kind of follow
along as you guys progress.
Dr. Webber (32:05):
Yeah, I appreciate that.
It's, you know, it's fantastic.
Come here and talk with you.
And I never turned down a chanceto talk about our work because
of.
Because of how much I know thatthis, you know, the stuff we're
doing means to people and also,you know, talking with you and
we know, and meeting yourlisteners and other sorts of
people really helps inspire thework we do.
And I get to go back and tellthe team about the people I meet
(32:25):
and the stories I hear and youknow, how the things they're
doing are, you know, beyond justthem in their thesis research or
the next paper, they want towrite that.
We're really thinking about howwe can bring something to
fruition that.
That could really have an impactin people's lives.
And so I think that really addsmeaning and adds value to the
things we do for sure.
And so I, I love having thesekinds of conversations, so I
(32:45):
appreciate the opportunity totake it, to talk about what we
do.
Katie (32:49):
Yeah, I'm just curious.
Does anybody on your team havetype one diabetes?
Dr. Webber (32:52):
Yeah.
I have one person on my team andI was type one diabetes.
And you'd believe.
He's one of my only ones thatdoesn't work on a diabetes
relevant research project.
Katie (33:00):
Yeah.
Dr. Webber (33:01):
I, I gave, I gave him the option and he basically,
you know, when he started and hesaid, you know, that's kind of
like everyday life for me.
And if you don't mind, I'dprefer to do something that
wasn't, it wasn't so personal.
And I said, yeah, then that'sperfectly fine.
And so so he's got a greatproject on.
You know, materials that couldthat could be triggered in the
presence of localizedinflammation in the body and
(33:22):
deliver drugs to localized areasof inflammation, which may be,
would have a role in, you know,autoimmune types of diseases
like diabetes, but maybe, youknow, other things as well.
Katie (33:32):
what did you call it earlier?
The it's the response likeyou're all of the things you're
working on in your lab, typeone, diabetes, diabetes related
or not, they all have to do withsensor responses.
What did you call it?
Dr. Webber (33:44):
Yeah, like stimuli, responsive materials is really
sort of our interest.
And so I'm, I'm bored by thingsthat don't move.
I'm bored by things that juststay static.
And so I really like things thatcan undergo interesting changes
as, or as a result of somestimulus.
And so these are, are materialsthat have always just kind of
excited me.
How can we engineer things thatcan, that can have a
(34:04):
communication with the livingworld can talk to things like
blood glucose or to cytokines orto you know pH or other sorts of
triggers that are relevant fordifferent diseases.
And how can we use those to thendrive changes in materials in a
way that would be responsive tothose needs?
Katie (34:21):
Amazing.
You guys are brilliant.
I love it.
thank you again, Dr.
Webber, and I'll be definitelybe keeping up with you.
I'm interested to see where thisgoes.
Dr. Webber (34:28):
No.
Thank you very much, Katie, forthe chance to talk to you, it's
been great to about our work, soI appreciate it
Katie (34:34):
Yeah, you're very welcome.
You have a nice week.
Dr. Webber (34:36):
And DTS you as well.
Katie (34:38):
Thank you.
And that's a wrap.
You guys know what to do head onover to the show notes and look
for all the links.
I'll put a link to where you canlearn more about what Dr.
Weber in his team is doing overat Notre Dame.
I'll put a link to the productfeature of the week, those
little four ounce plastic juicebottles, a link to buy me a
coffee, if you want to supportthe show so I can keep bringing
(35:01):
awesome content to you each andevery week, and probably a link
to something else.
Just check it out.
It'll be a surprise when you getthere.
I hope you guys had a greatThanksgiving.
Thanksgiving was last week and Ireally hope you took the time to
listen to diabetes, the musical.
I hope that put a little pep inyour step, this holiday season,
and I hope you are going to besinging your way through the new
year.
All right guys, have a fabulousweek and I'll talk with you
(35:22):
soon.
Bye.
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On Purpose with Jay Shetty
I’m Jay Shetty host of On Purpose the worlds #1 Mental Health podcast and I’m so grateful you found us. I started this podcast 5 years ago to invite you into conversations and workshops that are designed to help make you happier, healthier and more healed. I believe that when you (yes you) feel seen, heard and understood you’re able to deal with relationship struggles, work challenges and life’s ups and downs with more ease and grace. I interview experts, celebrities, thought leaders and athletes so that we can grow our mindset, build better habits and uncover a side of them we’ve never seen before. New episodes every Monday and Friday. Your support means the world to me and I don’t take it for granted — click the follow button and leave a review to help us spread the love with On Purpose. I can’t wait for you to listen to your first or 500th episode!
Las Culturistas with Matt Rogers and Bowen Yang
Ding dong! Join your culture consultants, Matt Rogers and Bowen Yang, on an unforgettable journey into the beating heart of CULTURE. Alongside sizzling special guests, they GET INTO the hottest pop-culture moments of the day and the formative cultural experiences that turned them into Culturistas. Produced by the Big Money Players Network and iHeartRadio.
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.