#1817 Transplanting Islet Cells with Piotr Witkowski, MD, PhD
Scott talks with transplant surgeon Dr. Piotr Witkowski about islet transplantation, early results with tegoprubart, regulatory roadblocks, realistic timelines, and where this research could lead. Learn more (Best on a laptop or desktop).
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Key Takeaways
- Regulatory Hurdles: Pancreatic islet transplantation is currently restricted in the US because the FDA regulates islets as a drug, requiring rigorous phase trials, unlike other countries where it is treated as an organ transplant.
- A New Breakthrough: A novel anti-rejection medication, tegoprubart (delivered via IV), is showing remarkable success in protecting transplanted islets without the severe toxic side effects of traditional immunosuppressants like tacrolimus.
- Advocacy is Crucial: Efforts led by Breakthrough T1D (formerly JDRF) and patients aim to urge the Department of Health and Human Services (HHS) to adjust regulations, unlocking insurance reimbursement and making the procedure a standard of care.
- Managing Expectations: While current trials show promise for desperate patients—especially those suffering from severe hypoglycemia unawareness—this procedure is not yet a widespread "cure" and is not currently available for children.
- The Ladder to a Cure: The eventual goal of islet transplantation research is to refine the procedure to a point where no long-term immunosuppression is necessary, paving the way for future unlimited stem cell-derived islet therapies.
Resources Mentioned
- Dr. Piotr Witkowski's Clinical Trial Info: pwitkowski.org
- Contour Next Gen Blood Glucose Meter: contournext.com/juicebox
- Medtronic Diabetes (MiniMed 780G): medtronicdiabetes.com/juicebox
- Breakthrough T1D (formerly JDRF): breakthrought1d.org
- The Human Trial (Documentary): Mentioned as a highly recommended watch to understand the clinical trial process.
- Defining Diabetes Series: juiceboxpodcast.com (Click on Series)
- Wrong Way Recording (Podcast Editing): wrongwayrecording.com
Introduction & Meet Dr. Piotr Witkowski
Scott BennerHello, friends, and welcome back to another episode of the Juice Box podcast.
Piotr Witkowski, MD, PhDDoctor Piotr Witkowski, I'm a I'm a transplant surgeon and professor of surgery at University of Chicago.
As attending surgeon, as a director of pancreatic islets transplantation surgeon.
I've been doing kidney and pancreas transplant and running clinical trials in islets transplantation optimizing the procedure.
Scott BennerAt the end of this episode, the doctor will share a website where you can learn more about his trial and if you are eligible.
He asked me to let you know that the website is best viewed on a computer or a laptop.
Doesn't really work too well on a cell phone.
So when you head over there, use your computer, your laptop, stay off that cell phone.
While you're listening, please remember that nothing you hear on the Juice Box podcast should be considered advice, medical or otherwise.
Always consult a physician before making any changes to your health care plan or becoming bold with insulin.
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Piotr Witkowski, MD, PhDI'm doctor, Piotr Witkowski.
I'm a I'm a transplant surgeon and professor of surgery at University of Chicago.
I was, educated and trained in Poland as a general surgeon, and I came to United States to do some research.
Initially, I I was involved in in research related to transplantation, different way to develop, the way to transplant organs without immunosuppression.
We call it tolerance.
I did my research at Columbia University in New York.
At the same time, I was involved in, in islets transplantation.
My mentor got a grant, and and we've been developing islets transplantation procedure or operate operation over there.
And then, after that, I accomplished training in in in a in a surgical training in transplantation, Columbia Presbyterian.
And after that, it was seventeen years ago when I came to Chicago as attending surgeon, as a director of pancreatic islets transplantation, surgeon.
I've been doing kidney and pancreas transplant and running clinical trials in islets transplantation optimizing the procedure.
So it's been seventeen years at the University of Chicago.
Scott BennerHow many iterations do you imagine that that procedure has gone through in that time?
Piotr Witkowski, MD, PhDHow many alternations?
Scott BennerHow many times has it been improved or updated or changed from where you started?
The Regulatory Hurdle of Islet Transplantation
Piotr Witkowski, MD, PhDSo this been a problem because pancreatic islets, which we isolate from deceased donor organs from pancreas, has been regulated in The United States as as a drug.
So, it was twenty six years ago when they they optimized eyelid isolation technique and eyelid transplantation procedure in Edmonton, Canada, achieving great results.
We wanted to adopt it right away, but then FDA said, no.
You have to test it as any other new drug in control environment and perform phase one, phase two, phase three clinical trials.
And when you do clinical trials, you have to do everything the same way because you testing the islets as a drug, which should be manufactured every time the same way.
And it took us over fifteen, eighteen years to accomplish those trials.
And over this time, we couldn't really modify anything only because it's been regulated as a drug.
Scott BennerThat time there was you trying to satisfy the FDA's ask?
Piotr Witkowski, MD, PhDRight.
Scott BennerOkay.
Piotr Witkowski, MD, PhDRight.
Over this time, the islet isolation technique hasn't changed.
Actually, it hasn't changed for twenty six years because we couldn't do it.
We have to do it in the one standardized way
Scott BennerMhmm.
Piotr Witkowski, MD, PhDTo satisfy FDA.
We've been changing and optimizing clinical part, the, you know, changing immunosuppression, replacing one immunosuppression with the other to to to achieve better results, but we couldn't really optimize.
And then because it was still all these years, it was clinical research, very expensive clinical research, the number of the patients which we were enrolling was was low, and therefore, we couldn't even modify the clinical part much.
Learn I mean, change a lot because of of limitation in in in in funding and and then in in patient number.
So the regulations which we apply in The United States and only in The United States has been not really helping the progress in the field.
In other countries, Canada, Europe, Australia, ILETS has been regulated as any other organ for transplantation, And and and it it means that every procedure is driven by the physicians, and and it can be developed changed all the time, optimized all the time for the optimal outcomes.
Scott BennerAre there other people around the world doing the same work and and able to move and iterate more quickly?
Piotr Witkowski, MD, PhDRight.
So for example, in Edmonton and Canada, they've done, over 700 eyeless transplant over the last twenty years.
In Europe, they did over thousand transplants, and they have this approved in England, in UK, in France, in in, in Switzerland.
It's a standard of care procedure based on the results from our clinical trials.
And we in The United States still cannot still have it approved because, again, it's a it's regulated as a drug, and it requires special conditions, validations, funding, liability, and it's it's way beyond the capability of of academic institutions.
Scott BennerTo reach that.
I I mean, I hear how frustrated you are.
I mean, did you go back to the FDA and explain to them why and what Yes.
Piotr Witkowski, MD, PhDSo for the last five years, we've been talk we've been publishing.
We've been presenting scientific data and advocating for adjustment in the regulations since for last five, six years.
First, it was COVID, which was the obstacle.
FDA was was focused on COVID.
After COVID, the regulators were not keen on any changes Mhmm.
Despite the fact that there is no no transplants as a standard of care.
No islets are available outside the clinical trials, and there was no progress.
So we've been publishing articles.
We've been we voice our concerns, and there was no really traction until recently when breakthrough t one d, the major foundation supporting type one diabetes got involved and now and our patients and social media, and now there is a hope that this this regulatory adjustment may happen.
Based on current law and regulations, the secretary of HHS has authority to adjust the regulations himself based on the feedback from FDA and HRSA, but but it can be done quickly and efficiently.
We are ready to work with regulators on proper adjustments, which will allow islets transplantation to be, on the one hand, available to patient as a standard of care, but still safe and an effective procedure.
So all the safeguards are are in place to reassure that it's done in the safe way.
Scott BennerIf health and human services made that change for you, how would that change what you're doing right now?
Piotr Witkowski, MD, PhDSo the major change would be this, that if islets are regulated as organ based on covered results, we can go to insurance and and show them the results.
And I know that they will, they like them because I already showed them to several medical directors of the insurance, and they said we will pay as long as regulations allows for this that your product is it's approved for clinical use.
So once the islets are regulated as organ, our product would be approved, and then it can be reimbursed.
Once it's reimbursed, we can do many more patients.
I mean, we can offer this procedure to many more patients, and then we can do many more studies and enroll patients faster and learn faster and progress the field.
And we can test the new ways, optimize the islet isolation, optimize the clinical protocols much faster, much more efficient, and and create progress.
Scott BennerSo right now, you're kind of stuck doing a clinical trial.
But if they changed it, you could just start doing the procedures, it would work for people?
Piotr Witkowski, MD, PhDOn one hand, we can start doing the procedure based on the our current experience
Scott BennerMhmm.
Piotr Witkowski, MD, PhDUsing approved medication.
At the same time, we can start continue doing clinical trials, and we will be testing new medication, less toxic, more effective medication is still clinical trials, but only a small fraction of those procedures will be paid by the research and everything else, the core of the procedure, which is standard of care, will be paid by the insurance.
Yeah.
So for example, with the same funding which we're getting from breakthrough t one d to transplant 10 patients, we can transplant 100 patients with the same funding.
So this will be a major change.
Scott BennerBe a little cynical for a second and tell me why you think set up like this and why it hasn't changed.
Piotr Witkowski, MD, PhDPeople who we talked to, were not focused on this.
They were always like, there are there are so many different problems.
We have to focus on something else.
I mean, what can I tell you?
Yeah.
There was no traction so far, but now there is traction.
And I think also that what's trigger changes now that we testing new medication, less toxic, patients are doing much, much better than before.
Mhmm.
So before was the general feeling is that Eyle's transplantation, well, they can help some patients, but there is so much side effects of of immunosuppression that the end of the day, it's not so beneficial.
So people were skeptic about the Ehlers transplant.
Now seeing how seeing patients with improved with reverse diabetes without side effects patients, people are excited about it.
So I think we brought it to the different level of efficacy and safety, and this triggers that that people are interested into this and see this as a chance for on the path to the cure.
Yeah.
And the ultimate goal is to to remove the need for immunosuppression.
But to get there, we have to go step by step.
We have to use better medication and then and then less medication, lower doses and and stopping the medication.
But it requires, you know, clinical testing before we are completely can can do it without immunosuppression.
Tegoprubart: A Breakthrough in Immunosuppression
Scott BennerSo is what you're saying is that the the tego prubart is that how do you say it?
Tego prubart?
Piotr Witkowski, MD, PhDTego I don't know why they come in with those names.
Tego prubart.
Yes.
Scott BennerTego prubart.
The understanding is that could be used in your procedure changes the feeling to people.
Piotr Witkowski, MD, PhDYes.
Scott BennerTaking it from, like, well, sure, we can do it, but you're gonna just trade one problem for a different problem.
Exactly.
Right?
Exactly.
And now it doesn't feel like that anymore.
Piotr Witkowski, MD, PhDRight.
Right.
Exactly.
So with with the tacrolimus, which is great medication, allowing us to keep the organ transplantation working for many, many years, but the trade off was that there was toxicity to the kidney, to the brain, to the nerves, to causing hypertension, causing diabetes.
So there there was a a trade off.
But we didn't have better medication over the last thirty years.
And now with tegoprobar again, these are the very preliminary results.
We have only 12 patients and and short observation, but all the patients do not have those side effects.
They don't have any side effects so far.
And they have, Ehlers transplant successful, and they they reverse diabetes.
So that's why you hear from patients that they feel cured because they don't feel burden of this therapy so far.
Scott BennerYeah.
What is the Tego doing that's allowing it to target this situation without suppressing the rest of your immune system so much?
Piotr Witkowski, MD, PhDRight.
Right.
So it is still suppressing the rest of the immune system, but the way it's suppressing is is more selective.
It's it's more accurate.
It's not, let's say, it's not as global as as the other medication.
The other medication, they're targeting many differ entire immune system and and many different checkpoints.
And then this medication, it's it's just one one main still main mechanism of rejection, but only one.
So the other is still working and and protecting patients and not causing the side effects.
So it's it's much more selective.
Okay.
And therefore, toxicity is so far, it's negligible.
Scott BennerMhmm.
But now this medication's being delivered every twenty one days through an IV.
Is that right?
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Piotr Witkowski, MD, PhDSo far.
Right.
So far.
And, again, we had to start with something.
Right?
Mhmm.
So the the delivery is inter intervene intravenous infusion.
It's reliable.
This is something is done, you know, here in in in our infusion center, so we know is the liver properly.
But moving on, you know, the company is already working on subcutaneous infusion I mean, injection by the patients.
Mhmm.
And then the frequency on injection can change.
The dose was was just the with was just a start was was actually, the dose was just proposed.
We're using the proposed dose.
We can based on experience, we can learn that the dose might be too high.
Right?
And we may go with lower dose.
So the dose might be adjusted or needs to be higher.
We'll see.
But that's why I'm saying it's just the beginning.
But, eventually, the there is a a good chance that this medication will be given by the patients themselves at home.
Scott BennerMaybe no differently than how people give them GLP shots.
Piotr Witkowski, MD, PhDYeah.
Exactly.
Like, once a week or once a month.
Exactly.
Yes.
Scott BennerWhat do you think the time frame is for that?
Has has that company given you any idea?
Piotr Witkowski, MD, PhDNow the company
Scott BennerIs that Eladon?
Is that the name of it?
Piotr Witkowski, MD, PhDYeah.
The the company is Eladon, and they're working on this.
They know about it.
They're working on this.
They're getting ready.
It's hard for me to say when, but but it's not far.
It's not far.
Scott BennerIs it I know that it's not your company, but can I ask you, is there a way to you know, with people who have so many different autoimmune issues, RA, for example, do you think there'll be injections that maybe we'll be able to more surgically target other autoimmune issues?
Piotr Witkowski, MD, PhDYes.
Yes.
As you said, actually, the this medication was the first tested with other immuno ALS, other autoimmune disease.
And any immunosuppression used for autoimmunity we test in transplantation or anything developed for transplantation is tested there because the mechanism is is very similar.
So definitely very similar.
Maybe this way, the drug with the same mechanism developed by Sanofi, and they're testing this for autoimmunity, and now they're thinking to come back to transplant.
So it's not only Eladon.
It's gonna be Sanofi with very similar medication.
And they already has sub q formulation.
Scott BennerOkay.
Oh, do they?
Sanofi does.
Yeah.
Yeah.
So this could really change, like, the face of transplantation to
Piotr Witkowski, MD, PhDI feel that this is this is a major change after thirty years because this is what I exactly feel comparing when I see patients on tacrololus on daily basis after kidney, pancreas transplant.
I see those pay after the heart transplant, amount of work on us and the patients to adjust the dose.
And the patient needs frequent blood test to change and control the level of the medication, and then we're changing the dose up, down.
Mhmm.
Patient's getting confused.
And despite change those changes, patient experience side effects.
It's a lot of a lot of work, a lot of frustration.
And now in the study with tegoprubar, there is no adjustment in dose.
There is nothing.
Yeah.
We just shake hands.
We hug.
How is everything?
Everything is fine.
From this perspective, it can change.
Less toxicity, less side effects, less less work on the patient and physician side to adjust the the dose of medication to to to treat or prevent the the side effects.
So this will change not only islet, it will change the transplantation.
Of course, assuming that nothing bad will happen.
Right?
There there will be no sudden unexpected adverse event.
And I can tell you historically, this medication was developed twenty five years ago in animals, and the results in animals were amazing.
But when it was used for kidney transplant in first three patients, all of them develop blood clots, which immediately the study was closed, and this was something nobody predicted.
So it took twenty five years for this the same medication to be modified not to cause cause the blood clots, SSI defects, and now we can we can we can use it.
So this is just example that despite, you know, extensive testing in animals, something may happen in humans which we couldn't we couldn't predict.
So far, it's good.
Scott BennerRight.
Piotr Witkowski, MD, PhDSo we have patient the the the first patient, the longest follow-up, almost two years.
Wow.
And there is patients beyond two years in the kidney trials, and so far, so good.
For our patients, we will be extending the the tegoprobar therapy for the third year for the and watch them longer to get more experience and learn more.
Scott BennerBut it's a miracle that the company kept going for all that time after the blood clots.
Piotr Witkowski, MD, PhDRight.
Right.
I mean, they were persistent.
Scott BennerYeah.
Somebody really believed in what they saw.
Yeah.
Piotr Witkowski, MD, PhDYes.
And the reason is because we saw amazing things which we never seen before in animals.
So that's why we were so excited.
And and and the company and we and others believe that if we overcome the side effects, we can still benefit from this mechanism and and for low toxicity.
The Future of Islet Supply and Encapsulation
Scott BennerYou get over these humps.
Let's just say it's an approved thing and you can start doing as many of them if you want.
I mean, how many islet cells are actually available?
Like, how many people could you actually accommodate if it got to that point?
Piotr Witkowski, MD, PhDYou mean from deceased donors.
Right?
Before the stem cells.
Because we still, need as yeah.
This is the question where you're going.
Right?
The the limited, number of deceased donors, limited number of islets.
The goal to have the updated regulation and keep doing disease donor islets transplant is to help the most desperate patients improve their life, reverse diabetes, and learn and learn a lot and progress the field in order to to minimize immuno or eliminate immunosuppression.
Now in the meantime, of course, we want to help patients.
Now how many patients?
We are able to do do I mean, we are limited by the funding and the money.
There is a 1,000 pancreas transplant done every every year in The United States, and they're using the best organs from one perspective.
The organs the pancreas which we use for islets are different than organs used for whole organ transplantation, so it's not competitive.
So let's say I mean, you know, nothing will happen overnight.
Right?
But, like, today, we are the only active center.
City of Hope is another one doing one or two transplant, and we do 30 transplants.
So today, it's like 40 transplant a year in the entire country.
Yeah.
But we can do, let's say, a thousand.
Right?
So thousand is much more than than than 40.
Right.
It will progress the field, oh, extremely
Scott BennerMhmm.
Piotr Witkowski, MD, PhDIf we can do a thousand.
It's not as a solution for every type one diabetic.
Scott BennerRight.
Piotr Witkowski, MD, PhDBut we can sort it out the way to minimize immunosuppression when the cells when when the stem cells islets are available.
We can just combine this new stem cells islets, which are in unlimited supply with minimal immunosuppression or or no immunosuppression, which we will work out using disease on our islands.
Scott BennerSo if to paint a picture for people, if you kind of go back to where the doctor was talking about starting twenty five years ago and think of this as a ladder to an eventual cure, which is when people talk about it, you know, in everyday life, that's what they're talking about.
They're like, give me a pill that shuts this off and right and it ends.
Right.
This thing that you're doing right now is huge.
It's a big deal.
It's amazing at how well it's working.
But even if you perfect it, it's just another step on the ladder.
Is that right?
Piotr Witkowski, MD, PhDIt's another step on the ladder.
But what I want to highlight in this medication in animals Mhmm.
We were able to maintain the kidney and islets function only with one medication.
In the tegoprobar trials, we're using thymoglobulin.
We're using my my my 40 additional medication.
So that is more than tegoprobar to protect the islets.
We saw in animals that just tegoprobar can protect it, so there is space to minimize immunosuppression.
Now once we stop tegoprobar in animals, the organs will keep going for several months.
So tegoprobot provides some kind of modulation which may allow for tolerance for no immunosuppression, let's say, after a year or two.
Understood.
But in order to to do that, we need develop a new monitoring system of the islets gram function.
So once we start reducing the dose, we need to know if islets are being compromised or not before they're gone.
Mhmm.
We don't want to expose patients to lose islets overnight only because we lower the dose.
So in order to do it, we we need more.
We need tools to money better monitor islets function, which we don't have today.
But this is the ultimate goal just to do it the way that no immunosuppression in the long term is necessary.
Scott BennerIf there's an eventual end to this, do you think it's found through medication, or do you think it's found through encapsulation?
What do you think is the best way to put
Piotr Witkowski, MD, PhDSo, yeah, how I'm gonna put it.
Today, for cadaveric islets, they need a lot of blood supply instantly in order to survive.
Any encapsulation, any additional layer separating the islets from blood supply, and this is what capsules do Mhmm.
It's just killing the it's it's just compromising their survival.
So I do not believe that encapsulation is the solution.
Okay.
Because they need blood supply.
Now for the stem cells derived islets, they might be more resistant.
They may need less blood supply.
Maybe there are new materials.
Maybe it will happen.
But I know from the theoretical perspective, you are doing something opposite than you should.
Islets needs a lot of blood supply, and you should improve blood supply rather than limit the blood supply.
Therefore, I don't believe in an encapsulation immunosuppression.
Now genetic modification, people are trying to modify them so they're invisible to immune system and avoid this.
I think it's gonna be difficult because we know only small part of of biology, of human physiology, immunology.
We know something, but we don't know everything.
And e and we can overcome some obstacles which we know about, but there might be another pathway which we don't know today, which will be causing the rejection and destruction.
Scott BennerRight.
Piotr Witkowski, MD, PhDFor example, today, all this immunogenetic modification to make them invisible to immune system is basically targeting the the rejection, but not really helping from to protect from autoimmunity, which kill the islets at the very beginning.
So we're not sure how to gen what would genetically modify to protect them from autoimmunity.
Scott BennerRight.
Piotr Witkowski, MD, PhDSo it's not close.
It's far in my mind.
Yeah.
It doesn't mean we shouldn't try.
Scott BennerNo.
No.
Piotr Witkowski, MD, PhDOf course.
That's why I'm focused on on on tegoprobar because this is something we can have today and tomorrow to help the the most desperate patient.
Scott BennerFeels like a more quicker, more direct path to you.
Piotr Witkowski, MD, PhDYeah.
Yeah.
Yeah.
I mean, it's something something we can do now Tangible.
Before before the other stuff is developed and stuff.
Defining a Cure and Setting Expectations
Scott BennerAnd good for everybody else doing that other work.
But like you said, that's if you find a way to protect the cell but don't shut down the immune response, you could just end up with type one diabetes again with the new cells.
Yeah.
Yeah.
Yeah.
My gosh.
Let's shift gears for half a second.
I wanna ask you more of a kind of a big picture question.
Your work is getting shared online a lot right now.
And I think it's exciting, and I love that people are sharing what's going on.
But from my perspective, I'm a person who's been making this podcast for twelve years, and it's focused on helping people take good care of themselves.
I get worried sometimes that people see this and think, oh, it's all done.
They fixed it.
I don't have to take very good care of myself.
It's almost over.
I wanna know if you have that concern or and if you can speak to directly to those people and tell them what's the the realistic timeline between what's happening right now on your bench and that random person who is not having dire health issues right now showing up in an office, getting this procedure, not having to take insulin anymore.
Piotr Witkowski, MD, PhDNo.
No.
Absolutely.
Absolutely.
Patients should take care of themselves and keep themselves as healthy as possible that when one day the real cure is available, they will not have problems.
Right?
They will be still seeing, have a vision, don't have amputations, don't require amputation or heart attacks.
So no.
No.
Definitely, patients should should do the best they can to stay as healthy as possible when the cure comes one day.
What we do, I want to highlight, it will help the most desperate patients in a limited number until we get there.
And it's still I'm not saying five years.
It might be much longer.
Yeah.
So, no, this is just what you're seeing and hearing is just impression from patients who feel great.
Right?
Mhmm.
But we can apply it to everyone today.
Yeah.
We cannot.
We don't have the the means and and technology, and it's not safe for everybody.
Right?
Scott BennerWell, I thought I was gonna say, it's a small group of people from a highly curated group of people too.
Right?
Piotr Witkowski, MD, PhDYes.
Yes.
Yes.
So the outcomes are better and the patients are happy, but it doesn't mean we can offer this to everyone.
Definitely not.
And I'm not sure when, and and people should stay as healthy as possible.
Right.
Definitely.
Scott BennerThere is even even a world where if their health has waned and this becomes easy and plentiful, you could get your health outside of a range where you wouldn't be eligible for it if that was Yeah.
Piotr Witkowski, MD, PhDYeah.
Yeah.
And and and and you will not even if you get it, you will not benefit, know.
Scott BennerRight.
Piotr Witkowski, MD, PhDThe way you could, you know, without secondary complications.
Scott BennerMhmm.
What do you consider a cure?
Like, what would you be comfortable not saying functional cure or this is better than it was before?
No.
Piotr Witkowski, MD, PhDI mean, I would think the same way as as as most people think that, you know, take a one magic pill or one magic injection infusion, whatever it it is.
And be sure that I will never had diabetes anymore, and it will never come back, and I don't need have to worry about some side effects.
Right?
So so in my mind, this is cure.
Right?
So I'm I'm a surgeon.
Right?
So if I remove the gallbladder, I know there will be no gallbladder disease For hundred percent, there might be other problems in the disease, but no disease.
So yeah.
No.
In my mind, the ultimate cure is something which can reverse diabetes in the consistent way forever without any side effects.
Scott BennerRight.
And that's what a cure is to you.
Piotr Witkowski, MD, PhDYeah.
Scott BennerYeah.
I agree.
Piotr Witkowski, MD, PhDBut then I'm sorry.
But I don't want to diminish what patients are saying.
Right?
They feel cured because they were diabetic with all the downside of this, and now they don't have diabetes.
And today, they feel cured, but they fully understand that tomorrow it may come back.
Right?
So but they're just describing the moment of happiness.
Scott BennerDo you think the work you're doing will lead to a broader understanding of the immune system in general and maybe help us to quell it to keep autoimmune issues down in people in general?
Piotr Witkowski, MD, PhDDefinitely.
Definitely, we would we can we can learn how to how to manage.
But to me, it's still hard to comprehend that in twenty first century, despite all those things, we don't know why autoimmunity happens.
Yeah.
And it's not only type one, any type of autoimmunity.
We don't know why people has Crohn disease, why there is theory.
There is, you know, this and that, but nobody can pin can pinpoint one one reason.
Right?
So I think this would be a major breakthrough if somebody will figure out why autoimmunity happens in the first place.
Because if we know the reason, we can prevent it rather than, you know, finding a cure how to reverse it.
Scott BennerYeah.
That would be lovely.
I talk to a lot of people every I mean, every day I record with somebody and and, you know, ask them about other autoimmune issues in their life or in their family line, and you can see it plagues families sometimes, you know, for all
Piotr Witkowski, MD, PhDdifferent Yeah.
Scott BennerYeah.
There there
Piotr Witkowski, MD, PhDis genetic factor for sure, but it's not only.
Scott BennerNot only.
No.
Of course.
Piotr Witkowski, MD, PhDThe best example in my mind is the ulcer.
Right?
The ulcer, this in the stomach for many, you know, thousands of years or hundreds of years, it's been the disease, untreatable.
And people were saying, oh, you have ulcer stomach because you're stressed.
Right?
Who is not stressed?
And people are trying to explain and treat it until the bacteria was suddenly discovered, which is causing this.
And we treat the bacteria, there is no ulcer disease.
I just hope that there's one thing which can be discovered and removed, and we don't have autoimmunity.
This is my hope.
Scott BennerRight.
Piotr Witkowski, MD, PhDI know people look into bacteria, viruses, and genetics, and diet, and and that, and and it doesn't look like it's a one single thing.
Maybe there is, and we cannot see it or find it yet.
Scott BennerMhmm.
I mean, it's it's interesting when you're trying to figure these things out.
I find it helpful to remember that we can use general anesthesia to put a person unconscious and that science doesn't understand exactly how it works.
That that that makes me some that puts a lot of things in perspective for me while we're trying to figure this stuff out.
You know?
Piotr Witkowski, MD, PhDYeah.
Yeah.
No.
No.
And and again, I I I'm in, you know, research and and medicine and stuff.
And the more I'm learning, the more I know that we don't know stuff.
Yeah.
The more we we we don't know.
Scott BennerCan I ask you a couple of bigger questions?
So you're how old are you?
Piotr Witkowski, MD, PhDI'm, how old I am?
57.
Scott Benner57.
How do you set your lab up so that your work continues on after you?
Is there a process in place for that, and how much of new AI models are you employing in the lab?
Those are kind of my two, like, questions about how you get to the end.
Piotr Witkowski, MD, PhDSo you see, I can do too many things.
Right?
I have to focus on something.
So my focus is clinical trials, execution of the clinical trials, optimizing clinical trials, and patient care, the patients who participate in clinical trials.
Mhmm.
So I do not work in, in my lab in basic I don't have a basic science research.
I don't develop, you know, something completely out of nothing.
The thing which will stay, I mean, after me is my experience Mhmm.
Based on patient treatment and adjustment in pay.
We're learning every days.
We are yeah.
New things about it.
And my role is to, you know, share with others, publish, and so that others can can benefit and take it to the next level.
Scott BennerYou're sort of a an artistic mechanic.
You take the parts that are available right now in the world, and you go into the machine and do your best to put it back together.
Piotr Witkowski, MD, PhDYeah.
Exactly.
Scott BennerYeah.
Yeah.
That's interesting.
Do you think that there's a way to pass your knowledge on to other people?
Do you have, like, people working with you who are learning from you?
Piotr Witkowski, MD, PhDOh, yeah.
Yeah.
Definitely.
This is especially in surgery, this is how he's been, you know, traditionally that we learn from our mentors, especially in surgery because, you know, there's a lot of details which is not in the books, you have to see and experience, and you learn a certain way.
And it's funny.
When when I was learning from my mentor during my fellowship how to do the kidney transplant, he was obsessed with the details.
Mhmm.
And I was always like, come on.
We can do a different or easier way.
Every time I deviated from his technique, his, you know, elements of the surgery, every time I got into trouble.
And I was developing discovering, oh, that's why he was doing this way.
Right?
Yeah.
He already went through this and optimized this procedure, and to me, it was that without any sense why he's doing this until I learned hard way that this was just based on the experience of he say, oh, personal experience, and I guess his mentor.
Scott BennerRight?
Yeah.
Yeah.
Piotr Witkowski, MD, PhDSo so so I'm going back, and I'm teaching my fellows in obsessed way.
I'm telling you, do this way.
You can choose your way, but I'm telling you this is better.
And you can do what you want with that.
Scott BennerIt's a classic parenting problem.
How do I get them to just believe me and move on?
Piotr Witkowski, MD, PhDThey need to get burned at least once.
Right?
Scott BennerThat just seems to be the human way.
Yeah.
Yeah.
To the artificial intelligence, do you have a feeling that it can move the understanding we have of how medications work or what we're seeing in labs?
Like, do you think it'll speed it up?
Is the bottleneck human beings somehow?
Piotr Witkowski, MD, PhDI think so.
I think so.
I think it will it provides additional tool beyond our comprehension.
This AI has has enormous power better than our brain so they can discover some connections which we don't see or cannot see.
So so definitely, it has potential to to extend the our vision,
Scott Benneryou know,
Piotr Witkowski, MD, PhDvision where we are and where it can be.
Scott BennerYeah.
I'm excited for that really to for us to be able to dump the collective knowledge of this kind of thing into one place and have something considerate that is maybe more likely to consider something we haven't figured out before or be able to think it through to a different end or something like that.
Piotr Witkowski, MD, PhDAnd there will be always people who will look outside the box and discover something by chance or by mistake.
Right.
And and and this is great.
Right?
This is this is the nature.
Sure.
Or discover something by chance.
But having this this special power of analysis beyond our regular, you know, power, this is this is amazing, and I think it will be helpful.
Scott BennerYeah.
Also, not having to eat, sleep, go home, talk to your spouse, take care
Piotr Witkowski, MD, PhDof your
Scott Bennerkids, like all the other things.
Right?
Piotr Witkowski, MD, PhDYeah.
Yeah.
The Cost and Realities of Clinical Trials
Scott BennerCan I ask you?
You said how ex that it's expensive to do the procedure, and you only have so much money to do so many.
Is there a way to generally tell me what the bill is on doing one of these for somebody?
Piotr Witkowski, MD, PhDYeah.
If you count everything.
Right?
Everything.
Like, if there is a program which want to start doing transplants and support the facility, the personnel with one source of money.
Right?
It's a lot of money.
So and, of course, the more you do, the cost per procedure is lower, right, because of the a lot of common costs.
800,000.
Scott BennerOkay.
Piotr Witkowski, MD, PhDThis is the for one trial one patient.
Scott BennerAnd that would cover everything Everything.
Soup and nuts.
Piotr Witkowski, MD, PhDAnd everything.
Right?
Yeah.
So if there is a center who wants to start running the program and do 10 transplants, they need 8 millions.
Scott BennerJeez.
That's something.
That's a lot to go going.
Piotr Witkowski, MD, PhDEvery because if you think about it, everything cost, and it's not only people, it has to be clinical grade reagents.
And they cost 10 times more than regular reagents.
Right?
Mhmm.
And then and then there has to be oversight, quality control, and there is so many elements.
Cell processing, and then in patient care, and then hospital, and then the medication are extremely expensive.
Right.
So this is all adding up.
But, again but I'm not saying that this is how much insurance should pay for one transplant.
This is not what I'm saying.
Because then, again, if you do more, the cost is lower and stuff.
Right?
I'm just saying for somebody who is starting and and and or doing on the small scale This is how you need this money.
Yeah.
To do to do a few patients.
Right.
To do a few patients.
Scott BennerIf you wanna open up your own McDonald's, this is what's gonna start to get it going.
Yeah.
Yeah.
Yeah.
And and to do and to do 10 patients.
Piotr Witkowski, MD, PhDRight.
So So your your your first hamburgers will cost a $100.
Scott BennerRight?
Right.
Yeah.
And eventually, you'll get it down to to scale.
Piotr Witkowski, MD, PhDYeah.
Yeah.
Eventually, you can you can take everything down and yeah.
Scott BennerYou have how many people on the trial right now?
Is yeah.
Are you on your thirteenth right now or you up to 12?
Piotr Witkowski, MD, PhDNo.
So so we got funding only for 12 patients.
Scott BennerOkay.
Piotr Witkowski, MD, PhDWe could do more, but the funding is was 12, and we transplant 12.
Scott BennerOkay.
Piotr Witkowski, MD, PhDWe are waiting for ethics committee, our IRB approval to start the second trial sponsored by breakthrough t one d for 10 patients, type one diabetes with kidney dysfunction with tegoprova.
Right.
So today, because of tacrolimus toxicity nephrotoxicity, we cannot do patients with kidney partial kidney dysfunction because then we will kill their kidney completely.
Mhmm.
So we cannot help patients with kidney dysfunction today at all.
So those poor patients, they have poor diabetes, and they have already kidney dysfunction, and they cannot get pancreas or islets transplant at all.
So this will be first time because of no toxicity of tegoprobar that we will be offering this group of patients islet transplantation.
We hope that the reversal of diabetes will stop the progress of the kidney disease.
And who knows?
Maybe it will reverse.
Maybe the kidney function will improve as it's been suggested by by some scientists.
Scott BennerInteresting.
Piotr Witkowski, MD, PhDSo this is coming for 10 patients.
Yeah.
Scott BennerYeah.
The first round is about proving it out in relatively healthy, you know Right.
Specific candidates.
Now you're gonna
Piotr Witkowski, MD, PhDrelatively healthy kidney and other elements.
Right.
But still with the hypoglycemia unawareness and severe hypoglycemia.
Scott BennerMhmm.
Then you move on to a a different group of people who have another issue.
If it works with them, then that's even more
Piotr Witkowski, MD, PhDexciting.
Proof that we can reverse diabetes in consistent way, more consistent than before.
Because before with tacrolimus, depending on the center, eighty percent of patients were 60 of patients were completely off insulin.
So the benefit was to prevention from hypoglycemia.
But once we prove that we can reverse everyone Mhmm.
For at least one year, then we I think we can offer the the procedure to patient without hypoglycemia unawareness.
For example, with a one c over seven, when we know that the the they have a higher risk of secondary complication and reversing diabetes will be beneficial for them even if there are some potential side effects from immunosuppression.
Eligibility and Managing Expectations
Scott BennerWhat's the youngest person you've helped so far?
Piotr Witkowski, MD, PhDSo yeah.
So we have two we have, you know, one patient in the study who is 19, and I have another 19 year old.
So the problem with teenagers is that they usually, you know, they not compliant with oral medication.
Right?
So you do transplant.
They're doing fine.
You ask them to take pills, and then they decide not to do it.
And they have rejection.
They're losing.
So, traditionally, we wait until 26 and older when they're mature, and we can rely on them taking the medication.
Now this this specific patient has a tremendous family support.
And also what convinced me that this tegopropart is IV.
So I'm rely I'm relying that the family will bring bring the patient to us, and and the patient will be safe getting the medication in the right way.
Scott BennerAnd if they're not there, you'll know they're not there.
You can get them there.
Piotr Witkowski, MD, PhDRight?
Then we know if something is wrong, we are alarming patient with the parents and and stuff.
So the fact that this is IV, and it's a it's a main medication, and there's, you know, devoted parents.
And the patient is also dedicated.
Don't get me wrong.
Yeah.
Scott BennerHe has the support structure.
Right?
He's not college student somewhere living in a dorm somewhere alone without Mhmm.
Supervision, and and then he may he may just just lose it.
Piotr Witkowski, MD, PhDRight?
So so so not yet.
Scott BennerAs much as that is about their health, it's also about you and your trial and getting back the information that you need.
Piotr Witkowski, MD, PhDYeah.
Yeah.
No.
Of course.
We want good outcomes.
But what really pushed me was that this particular patient had no life.
He because of severe hypos and poor glucose control, he had no social life.
He didn't go to college.
He's just sitting at home with no life.
Yeah.
So the life was so severely compromised that that I decide to to help him and and, you know, his parents and him.
And
Scott BennerIs the tego pro bart, is it eligible to be used in children, like, or
Piotr Witkowski, MD, PhDis I mean, no.
No.
No.
It's still under development.
Okay.
So in gen as a general rule, the medication are tested in adults first.
Scott BennerOkay.
Piotr Witkowski, MD, PhDAnd once they approve in adults, then depending on the profile and risk benefit, they can be, you know, considered for children testing in children.
Yeah.
But it's a it's a separate path, separate testing after approval for the adult.
Scott BennerAnd that's a time in the future.
But for you personally, have you seen enough to feel comfortable using it in kids, or have you not seen enough yet?
Piotr Witkowski, MD, PhDNo.
Not yet.
No.
I have to highlight that as much as we have great preliminary results, it's still under rejection medication.
Yeah.
So we don't have toxicity on daily basis, which we see with other medication.
But there is still potential for skin cancer in the long term.
The long term overall immunosuppression side effects, which is the skin cancer or the the blood disease like leukemia.
So, no, there is still potential risk in the future.
And until we don't have real experience and data, definitely, we shouldn't go to children.
Scott BennerYeah.
I ask you some of these questions just so the people listening can understand.
Piotr Witkowski, MD, PhDThe people are.
No.
No.
We're having, you know, emails every day from desperate parents and asking when and how because they're desperate.
We understand this.
But but the message is it's not for children yet.
Eyelid transplantation, yeah, is not for children because we're using toxic immunosuppression.
Scott BennerRight.
Piotr Witkowski, MD, PhDAnd then, it's not justified yet.
The Human Element of Clinical Trials
Scott BennerTaking the science out of it for a second, can you tell me a little bit personally how it feels to see somebody have this burden lifted from them?
Piotr Witkowski, MD, PhDOh, this is amazing.
This is what's driving all of us entire our team, you know, when we best reward is when we can tell patients you can stop the the pump.
And I don't know if you saw the post from yesterday because we stopped the part the the the insulin on on patients few days ago.
And every time is the same is the same excitement when they telling us, you know, some patients, they they were one year old.
They don't they don't know life without insulin.
Scott BennerSure.
Piotr Witkowski, MD, PhDAnd and suddenly, they can live without.
And one of the first patient when we told her, she was, like, 57, all life diabetic, and we told her she was so so emotional about this, and we were then we will let her go.
And she was running on the stairs, she fell, and she broke her arm.
So we felt so bad about it, and we blame ourselves that
Scott BennerShe was so excited she fell?
Piotr Witkowski, MD, PhDThat she was yeah.
She was so excited that she fell and she broke her arm and she needed surgery.
Scott BennerOh.
Piotr Witkowski, MD, PhDSo we decide to keep the patient in the bed, in the room for some time or tell them over the phone.
Scott BennerOne of those, is everybody sitting down?
Yeah.
Yeah.
Yeah.
Piotr Witkowski, MD, PhDSitting down and and then sitting down for a while and not just let them go right away.
Yeah.
No.
No.
I mean, on the one hand, telling patients over the phone, it's a safe way to do it.
Mhmm.
But then we're missing the, you know, the celebration and the the excitement.
And and it's all it's rewarding for our entire team because I don't know if you know, when we bringing the the pancreas, the seasonal pancreas to us, it usually arrives midnight, 1AM, 3AM, 4AM.
And my team is working usually at night, isolating whole night, eight hours, ten hours, sometimes two pancreas in a row.
So so there's a lot of dedication in the team.
Yeah.
And they do on they do it on weekends as well.
When the good organ comes, we are twenty four seven, and these are the same people.
I have only one team.
So there is a lot of dedication here, but but, again, it's all stimulated by by seeing our patients happy.
And that's why that's why we share our our joy with others.
And then what was triggered at the beginning was that I understood that the general perception of Eyelis transplant is that they don't work.
They just hurt patients, and we shouldn't do it.
That's why we start posting that this is not true, and it can be helpful, and it it can be a path for better therapy or cure in the future.
Scott BennerI can't imagine how busy you are.
You and I have been scheduled to do this since November, and it's it's April 1.
And November, December, January, February, March yeah.
Piotr Witkowski, MD, PhDNo.
Don't be
Scott Bennerdon't be sorry.
Piotr Witkowski, MD, PhDSomething.
Right?
Scott BennerYeah.
Know.
But I'm just saying there's a varied nature and a and a hurried nature to what you're doing, and it's a lot of effort.
I genuinely appreciate it.
I'm sure everybody listening does too.
Advocacy: How You Can Help
Scott BennerCan I ask you, is there something who people are politically minded?
Is there something that they could do or you need them to do to help with these cells and their availability, or is that being taken care of by the lobbying that breakthrough is doing?
Piotr Witkowski, MD, PhDThe breakthrough is doing.
Right?
But, but it's not done deal yet.
Right?
So so so definitely, we've we've been voicing our concerns to FDA first now to HHS directly.
In the meantime, since we didn't get attention, we couldn't get attention, we reach out to senators, and senator Mike Lee responded.
But now the the shortest path is through HHS.
And there is some attention, but it's just the beginning.
So Right.
I think, you know, if people can express support for what we're asking for for regulatory adjustments so it can be done safe and effective and available to to patients, this will definitely help.
Scott BennerI see.
That's excellent.
Piotr Witkowski, MD, PhDBecause HHS are are watching watching social media, watching what's going on.
Today, we don't live in vacuum.
I mean, for me, I knew social media is powerful, but I never thought that this will be the the the breakthrough through social media.
Scott BennerYou didn't think you'd be a guy being on podcast.
Piotr Witkowski, MD, PhDWe wrote papers for five years.
Yeah.
And we were writing about this for five years, and it's like any other news.
I mean, nobody's seen it.
Scott BennerNobody
Piotr Witkowski, MD, PhDpaid attention.
But now there is attention, and it's a good moment to to have it fixed.
Scott BennerThat's excellent.
Well, I wanna say that I have been for well over a decade when people would ask me why are you supportive of JDRF and now breakthrough t one d?
I would always say, am very excited about having an entity with lobbyists Yeah.
In government to know how to get to people.
Like, I think that's incredibly important.
I'm glad to see I was right because Yes.
This is fantastic news.
Piotr Witkowski, MD, PhDNo.
Definitely.
Definitely.
There is a gap, and they're filling the gap, and they it's critical.
It's critical to have stuff done in the right way.
And and Breakthrough t one d, it's it's a great advocate for this, and and we hope that this this issue will be also resolved.
Scott BennerCan I ask you a question that I'm sure some people listening are asking?
Why didn't you just leave America and do it somewhere else?
Piotr Witkowski, MD, PhDSo first of all, the America I mean, we in America have amazing infrastructure.
Mhmm.
So my advantage over European countries is that I, doing this, I have all deceased donors in the country available with, you know, over, what, two nearly 300,000,000 people.
I have so many organs available.
And living in Chicago, we have infra that you have flights.
We can bring the we have to bring the pancreas within twelve hours.
And living in Chicago, I can bring the almost from everywhere
Scott BennerOkay.
Piotr Witkowski, MD, PhDWithin twelve hours here.
So I have huge number of donors, which they don't have in the small small countries.
So I can do much more.
And, you know, infrastructure is is here.
Yeah.
I'm from Poland, so I help my university to develop the program, IELTS program in Poland, but they have own limitations, so it didn't really take off.
Scott BennerOkay.
Piotr Witkowski, MD, PhDBut they had the chance to do it.
So each country has only limitation.
More some of them are more or less successful.
But I believe I mean, this is the best place to do it.
Scott BennerOkay.
Piotr Witkowski, MD, PhDOnce we have the right frame, we can do it.
And we were leaders in the field when we were doing the trials sponsored by by NIH and and JDRF.
We were leaders.
We were doing there were, like, eight centers in The States doing this 300 transplants.
We've been optimized I mean, we've been doing stuff, and we were teaching others.
It's just that once the trials were finished, there was no system for support.
Scott BennerOkay.
Piotr Witkowski, MD, PhDThere were no reimbursement and no more funding for research, and all the centers just closed.
People who had experience in this disappear, and and then we lost a lot.
We lost not only time, but experience.
So now we have to rebuild it.
Scott BennerWe'll build that again.
Piotr Witkowski, MD, PhDWe will be leaders again.
We just need this as chance.
Scott BennerI believe that.
You just said something that has a question in my head.
I don't know how much it fits here, but you said the pancreas is often come in late at night.
Is that because they're donors and people have accidents later in the evening?
Piotr Witkowski, MD, PhDRight.
Because the the organ donation happens in the regular hospitals
Scott BennerOkay.
Piotr Witkowski, MD, PhDUsually after hours.
Right?
So first, they are got the the elective cases goes, and then the procurement happens in the afternoon or or at night.
Scott BennerI see.
Piotr Witkowski, MD, PhDAnd then it arrives to us at night.
Scott BennerOkay.
So if health and human services makes this adjustment to how this thing is designated, you can move forward as quickly as there's nothing standing in your way anymore.
So this
Piotr Witkowski, MD, PhDI mean, we would need to talk to the insurance and, you know, show them the data and convince them to pay.
Mhmm.
The argument from, from medical chief medical officer of one of the insurance, when he saw the data, he's like, this is no brainer for me.
Patients are not in the ICU.
Stay in the hospital for three days.
Go home.
They back at work after one week without diabetes.
Yeah.
This is a no brainer.
Scott BennerCan you speak to the to the people out there who would say, well, they don't want us cured because they're selling us insulin and pumps and all this other stuff.
Can you explain to them why that's not the case or is the case in your opinion?
The tinfoil hat, can you can you tell them how to take it off?
Piotr Witkowski, MD, PhDOh, no.
No.
How I'm gonna say it.
I mean I mean, we all know there is a pharmaceutical business.
Right?
There is pharmaceutical business.
How it interacts with political decisions?
Yeah.
I want to believe that everybody wants the best for the patients.
Okay.
Scott BennerThere's part of me that that I should be wondering a little bit if this stalling for the last twenty five years isn't somebody else's lobbyist being better than our lobbyist.
Is that about right?
Maybe.
You're not that you maybe you don't wanna say.
I'm not sure.
Scott BennerYeah.
Piotr Witkowski, MD, PhDI mean
Scott BennerWe got somebody on our side.
That's what I should think.
Piotr Witkowski, MD, PhDFor some reason, we are here twenty five later.
Twenty five years later.
Scott BennerI see.
Yeah.
Okay.
Well, so then the people listening to this, I mean, the call to action here is to contact health and human services and tell them tell actually, say it again.
Tell me exactly what you would need from them to make this valuable for you.
Piotr Witkowski, MD, PhDSo I think my understanding is that that HHS should hear from everybody that this is the right thing to do, not only us physicians and experts in the field, from patients, from endocrinologists, from everyone Mhmm.
And that that this is what is expected, and we all believe that is the right thing to do.
And and their job is to analyze it and frame it in the proper way that we all will benefit from this.
Scott BennerYeah.
The benefit there is to the insurance companies because if they can get somebody off of all those devices and those and then then they don't have to pay anymore.
Yeah.
You just have to create a Yes.
A benefit somewhere else.
Piotr Witkowski, MD, PhDAnd then my my message is is that we're not gonna remove need for devices.
The insulin pumps, closed loops, getting getting better, and they're helping majority of the patients.
And we will treat still treat the minority Mhmm.
Of the patients.
So we're not replacing islets transplantation.
We're not replacing the CGMs and pumps yet.
No.
Not not at all.
We'd offer this today for all those poor deaf desperate patients who suffer despite using, and they don't have, you know, life normal life despite using the pumps.
Scott BennerHelp the people who are suffering the most.
And hopefully, we we learn something along the way that allows us to help more people easier.
Piotr Witkowski, MD, PhDYeah.
Yeah.
Definitely.
Scott BennerOkay.
Because the procedure you have right now, even if everybody was out of the way, you're not able to stand up and say, okay.
There's two million of you out there with type one diabetes.
Everybody get in line.
We're all done.
You know what mean?
Piotr Witkowski, MD, PhDRight.
Right.
Absolutely not.
Right?
This is what we hope for, but no.
No.
No.
Scott BennerWe're not there.
Piotr Witkowski, MD, PhDI'm telling you, if we do a transplant, a thousand transplants a year
Scott BennerThat would be amazing.
Piotr Witkowski, MD, PhDI would be happy.
Right?
Of course, it may change.
Right?
Yeah.
Of course, it may change if suddenly we start doing a thousand and we optimize.
We develop new technique of isolation.
We figure out many different things.
It may it may scale up.
Right?
But we don't have it today.
I can't promise anyone that we will do, you know, unlimited amount.
Definitely not.
Scott BennerSomething almost unforeseen at this moment needs to change before you can scale like that.
Mhmm.
Okay.
Piotr Witkowski, MD, PhDOh, yeah.
Scott BennerYeah.
Yeah.
Piotr Witkowski, MD, PhDYeah.
So changing the regulation is the first step.
First step.
And and then it will be right environment and framework for people to do stuff.
Right?
And then we'll see.
Because if the stem cells therapy comes soon, right, we're not gonna have time to scale up disease donors.
The let's say, Vertex cells will will replace them.
They will be better, available, more consistent, and and available right away.
Scott BennerWell, that's very it's valuable.
And it it's important to me to to be very just transparent and honest with people because like I said, I Oh,
Piotr Witkowski, MD, PhDyeah.
Yeah.
Yeah.
No.
The I
Scott Bennerthink it's fantastic that people are sharing their stories.
I really enjoy seeing it.
But for everyone like me who sees it and says, that's amazing.
I think that's a great step, but we're not that that doesn't mean that three weeks from now, it's over.
Piotr Witkowski, MD, PhDNo.
No.
No.
For
Scott Bennerevery person Absolutely.
There's a lot more people out there who see that and just think, oh, gosh.
Piotr Witkowski, MD, PhDAs and if you look even this, you know, we're using tegoprobot in ten, twelve patients, but this is gonna take years again before tegoprobot is approved for everyone.
Scott BennerRight.
So And that's on the other thing.
Piotr Witkowski, MD, PhDHappens overnight.
It's just the beginning, and and and it's a good beginning.
Sure.
Scott BennerSure enough.
Piotr Witkowski, MD, PhDAnd the progress with with people I mean, with disappointment comes that they heard that in five years, we're gonna do this on that, or we're gonna get somewhere.
The progress, it's never linear.
Right?
It's not one line going up.
It's just like a step.
Yeah.
You're trying, trying, trying, and then you take a a step up.
Right?
And but you don't know when is your next step.
Scott BennerRight.
Piotr Witkowski, MD, PhDThere is a hope that we that the steps will be, you know, on a regular basis to get to the heaven Yeah.
In five years, but this is not how it works.
Scott BennerIt's not how it works.
Well
Piotr Witkowski, MD, PhDAnd I can't believe it because, you know, I've been I've been I've been here in this country and involved in Ireland for last twenty six years, and it's like yesterday.
Right?
So you you you're saying in five years, but how many five years I already haven't seen the progress.
Scott BennerSure.
Well, they've been telling people they've been telling people five years for fifty years.
Yeah.
Yeah.
I always imagine it's because the person working on at that time actually really is hopeful and thinks they see a an end to it.
I also think they probably want their research funded, so you say positive things while you're doing that.
Piotr Witkowski, MD, PhDOh, yeah.
No.
This is another thing that that people and companies, they they need the funding, and they sometimes exaggerate.
Right?
Scott BennerRight.
Piotr Witkowski, MD, PhDAnd people reading this, they really think and the one one thing just came to my mind, which is also related, is that when in in 2000 in the year 2000, when Edmonton group, they described seven patients of insulin for one year after eyeless transplant.
All of them of insulin.
Right?
Mhmm.
Is the moment when expectations were like, oh, come on.
This is what you say.
Oh, we have it.
Scott BennerYep.
Piotr Witkowski, MD, PhDOh, now now we're gonna roll.
Right?
In five years, everybody.
But then the immunosuppression was not sufficient, and they were gradually losing the insulin independence.
And and that's this is when the disappointment came.
Few years later, they were not more anymore.
Only only 7% were on the of insulin.
Right?
So people were saying, oh, no.
No.
You see?
I listen no.
I listen to
Scott Bennerwork and stuff.
Yeah.
Piotr Witkowski, MD, PhDBut this was all about the expectation.
The expectation were huge when it happened, and then it didn't meet the expectation, and then there was a huge disappointment.
Scott BennerAnd sometimes time just has to pass and different minds have to get set on problems and
Piotr Witkowski, MD, PhDRight.
But setting the expectations is important.
Right?
So when we talk to the patients, I'm I'm promising that we will work hard to get them there.
I can't guarantee that we will get them with every patient because every patient is different and and and and and some unexpected thing happen.
But I'm promising that we will work hard to and do everything we can to keep them safe and and get them off insulin.
But, but sometimes it's too much for some patients.
Right?
The the amount of adjustment and and oversight and going to the labs and this and that and experiencing complications, sometimes it's too much.
And they're saying, no.
No.
No.
This is too much for me.
Yeah.
So we are warning that this is a commitment on both sides, and it would require and you see, even the first patient from Tecoprubar, I don't know if if you've seen my presentation.
So the first patient was off insulin, and then she decided this is too much for her, come to Chicago every three weeks.
Mhmm.
And then she decide to switch to tacrolimus knowing that it's more toxic.
But regardless, traveling to Chicago was too much for her, which she didn't know before.
Yeah.
And you would think, come on.
I mean, you are off insulin.
You really want to risk being diabetic anymore?
But for her, it was too much.
It was too
Scott BennerAnd why could you not do the infusion where she was?
Piotr Witkowski, MD, PhDBecause this is experimental medication.
It has to be given here for the safety.
Scott BennerOkay.
Piotr Witkowski, MD, PhDIn the future, once it's approved, as we discussed, it can be infused at home.
It can be given sub q.
Definitely in the future, but not yet.
Scott BennerNot yet.
So almost like when I go get a an iron infusion, I go to an infusion center.
There are people there getting all different kinds of medications at that time.
Piotr Witkowski, MD, PhDYeah.
And then I don't know about the iron, but we have another medication, belatacept, which we're using in a which is approved medication, and then patients are getting them either in infusion center, as you said, or at home.
And then just come come to patient home, put IV, one hour infusion done.
Scott BennerI see.
Piotr Witkowski, MD, PhDSo we have similar medication, belatacept, which we which we use as well outside this trial for for our different trial, and it's it's working as well.
But the tacrolimus is given just in the lower dose.
So this medication cannot replace tacrolimus.
Can I mean, allows to lower the dose and minimize the side effects?
So, like, halfway what the the goprobar is allowing for.
Scott BennerAre you looking for trial participants right now, or do you have your next group?
Piotr Witkowski, MD, PhDNo.
No.
So so we look we're still looking for patients with kidney dysfunction.
Scott BennerHow can they get ahold of you?
Piotr Witkowski, MD, PhDSo on our website, there is a there is a link to the Eladon, the GoPruvat study, and they can follow the prompts to enroll into the study.
There is a questionnaire.
Mhmm.
They can fill up the questionnaire, and there is instruction where to send the questionnaire.
My nurses are reviewing every questionnaire, and they segregating the patients, those with normal kidney function and kidney dysfunction.
And we will be inviting patient with kidney dysfunction one after another until all the spots are filled, but we still have open spots.
Scott BennerAnd don't lie.
They can tell.
They're gonna check.
So Right.
No.
Piotr Witkowski, MD, PhDI mean I mean, again, it's it doesn't help because if they if they lie, they come here and the result is here.
So we cannot qualify patients with the results outside the range.
Scott BennerWhat's that web address?
Is it is it actually pwackowski.org?
Piotr Witkowski, MD, PhDYeah.
Yeah.
Yeah.
This is the website.
Scott BennerOkay.
I'll put it I'll put a link in here for you, see if we can get you those people.
Mhmm.
Yeah.
That that would be awesome.
Is there anything that I should have asked you about that I didn't?
Anything that you'd like to say that I just didn't get to?
Piotr Witkowski, MD, PhDIt was really comprehensive.
It was really good, and I appreciate everything you're doing promoting, you know, everything for for patients with type one diabetes.
Scott BennerThank you.
Piotr Witkowski, MD, PhDAnd and giving us a chance to to tell patients about about us.
I think, again, I'm not our patients, they posting what they feelings.
Mhmm.
It's not moderated by me.
I'm not involved what they're saying.
I'm not clarifying.
I'm not because I I don't think it's yeah.
So there might be, you know, some misunderstandings and stuff.
And at the end of the day, you know, we, you know, we are providing comprehensive information.
But the the bottom line is it is still anti rejection medication.
It's just less toxic than everything else we used before.
Mhmm.
And the patient tolerated tolerating this much better than everybody before, and the outcomes are better than every everything before.
But it's all preliminary all preliminary, and it's not final.
So we're still evaluating this.
Scott BennerBut a lot of reasons to be excited.
Piotr Witkowski, MD, PhDOh, yeah.
Oh, definitely.
No.
No.
We are so we are so excited.
Right.
And especially, I want to highlight that we as a scientist, we're testing new things.
And then often, it doesn't work.
Right?
So there is a lot of stress and and and disappointment on patient's side and our side.
Mhmm.
But this time, we are just lucky that the staff which we the approach which we testing is working better than anything else.
So this is this is extremely rewarding, stimulating.
And I don't know if you if you've seen the documentary, the the human trial.
Scott BennerI know of it.
I have not seen it.
No.
Piotr Witkowski, MD, PhDYeah.
I I I highly recommend it to to everyone to watch it.
It's a documentary about the patients who who participate in the ViaCyte stem cells islets transplantation trial when the stem cells islets were implanted in the plastic pouch and abdominal wall.
Mhmm.
But but the documentary is made by the director who is also type one diabetic, following the camera not only medical team, but patients at home.
And it allows us to better understand all these emotions and and everything related to to be a participant in the study.
Sure.
And it didn't work.
It didn't work.
So the the documentary shows, you know, the the pain, right, and disappointment.
Although they all highlighting the patients and physicians.
Yes.
Physicians told us it may not work.
We knew it may not work, but they still, you know, sacrifice years of laughs, of dry of emotions, and and and then and they it shows disappointment.
It shows disappointment that it may not be successful.
Scott BennerPeople's kindness supports this a lot.
I had a a woman on one time.
She I think was it Veritex, the one pouch or Viacyte?
Maybe.
I'm not sure I remember.
She was in a trial.
They couldn't even tell her she was for sure getting actual stem cells.
They just they needed to do it was a blind it was double blinded.
Piotr Witkowski, MD, PhDIt was blinded.
So She
Scott Bennerstill did it to help, which I thought was amazing.
Piotr Witkowski, MD, PhDIn this trial, they were not telling them if there is NSC peptide, if the islets are working.
They were not telling them.
Yeah.
So they were guessing.
Right?
And seeing those emotions, like, I feel like islets are working.
Oh, I feel better.
I feel but the uncertainty is still is still not allowing them to celebrate.
Scott BennerRight?
Sure.
Piotr Witkowski, MD, PhDAnd at the end, they learned that there's nothing.
Nothing works.
This was this was the hard part.
Right?
So I'm glad that we can tell patients, where they are, what's going on, and what they're getting, and and we can share it with others and and and go together along the way.
So
Scott BennerYeah.
So this is You threw something against the wall and it stuck.
Yeah.
That's awesome, Mike.
Piotr Witkowski, MD, PhDI can give you I can give you another example.
Scott BennerPlease.
So we've been testing, the Eilish transplantation into the the Cervova pouch, which is a a new experimental, and we were not sure if it's if it's gonna work.
Mhmm.
And patients require surgery, implantation, explantation, several surgeries.
So we were aware that this requires a lot of sacrifice.
So I was able to convince the the funding agency and the sponsors to add additional transplant into the liver if regardless, if the islets and the pouch doesn't work so they can get the benefit of participation in the study, but being off insulin with the islets and the liver.
And and then, and this is what happened.
The the results in the pouch were, you know, suboptimal, and they all received the islets and the liver, and most of them are off insulin enjoy enjoying the living without the without this.
Right.
Piotr Witkowski, MD, PhDAfter the sacrifice.
So this is what we learned from this documentary.
Right?
That we should provide patients more benefit rather than just telling them, I'm sorry.
It didn't work.
Scott BennerYeah.
No.
The living with diabetes is already a lot of mental and physical stress.
You don't need extra, you know, especially when in this situation.
Well, I I wanted to thank you too.
It was nice of you to say that the conversation was comprehensive, but I wanna mention that listeners of the podcast sent in a lot of questions for you, and I synthesized those questions down into the the road map that we followed today when we were talking.
And you were lovely to come on.
You weren't you did not have these questions ahead of time.
You're just sitting there listening and answering, and I thought you did such a wonderful job of outlining what all this is and and what it isn't.
I definitely feel very good about about the direction and and moreover that you're in charge of it because your passion and time, it looks like it's really starting to pay off.
And I I can't thank you enough.
You don't know this about me.
I don't have diabetes.
My daughter will be 22 this summer, and she was diagnosed when she was two, and she has type one.
Piotr Witkowski, MD, PhDOh, I'm really sorry.
Scott BennerThank you.
I appreciate it.
She's doing well, but I but I really do appreciate it.
Piotr Witkowski, MD, PhDBut no.
But, yeah, we all know how much, you know, how much work and how how challenging how much harder is life, basically.
Scott BennerIt really does reshape your life in a way that you would like for it not to have.
That that's for certain.
Piotr Witkowski, MD, PhDBut one more thing if I can share with you.
Please.
So all the patients when we telling them, now you're diabetes free, you're insulin free, go and enjoy your life.
Right?
Mhmm.
So they're happy.
Right?
But the next day they come, they're not happy.
I'm like, what's going on?
Oh, I have problem with my car.
I'm like, so so this happiness, which I thought gonna stay forever.
Right?
No.
These are regular people who has regular pro problems, and they have just new problems.
Right?
And and they're manageable problems.
Of course, they have perspective.
Of course, they do remember how life was miserable before.
Actually, many of them are forgetting.
And I and it's funny when I'm when I'm observing some of the patients when they when they're giving interviews, when they're being asked how was the life, they it's became, like, so distant.
They're not getting into details anymore.
Scott BennerDoctors like, listen.
Maybe I'm working too hard here.
I don't know.
Piotr Witkowski, MD, PhDI mean, one message is that that, you know, we you know, everybody has own problems.
Eventually, if it's not diabetes, there are other problems.
And then people what I also learned that people with diabetes Mhmm.
They more resilient after after that.
I mean, after being off insulin, they're also you know, the the regular life challenges are not not as stressful for many of them.
I But for for some of them, they they are.
Scott BennerComes right back.
I have to tell you doctor, I feel like I have the perspective of a 200 year old man.
Like, you know, seriously, like, my daughter being two years old and being diagnosed was was really through
Piotr Witkowski, MD, PhDa lot.
Scott BennerYeah.
It's something else.
And for her too, I she she sometimes seems to have the wisdom of somebody three times her age.
Piotr Witkowski, MD, PhDYeah.
And then I I can't even imagine how hard it is, you know, having a a child with diabetes.
It's challenging for others, but for children and
Scott BennerRight.
Piotr Witkowski, MD, PhDYou know, childhood, teenager, I mean, it must be.
Scott BennerWell So I'll say this.
This podcast exists because I taught myself how to manage insulin, and it turned out that it worked really well for her.
And then I realized that I had a way of communicating that information that allowed other people to just hear it and then kind of replicate it for themselves.
And this podcast over the last twelve years has close to 22,000,000 downloads.
Piotr Witkowski, MD, PhDWow.
Congratulations.
Scott BennerYeah.
Thank you.
And I'll tell you right now, the the feeling you get when you hear somebody say, you know, my a one c's in the fives or I haven't been in
Piotr Witkowski, MD, PhDlove you.
Scott BennerOh, it's it's just wonderful.
Right?
But at the same time, they do disappear.
They stop listening, you know, because they go they go back to their lives.
And and in the end, you know, what I wanted to share with you about it was I've come to think of that as, like, graduation, and I'm happy when when they're gone.
You know what I mean?
So Yeah.
Yeah.
Yeah.
Yeah.
If I was you, I'd be thrilled that they're worried about their car and they're upset about it.
Piotr Witkowski, MD, PhDOf course.
Of course.
Of Of course.
Yeah.
It was just surprise to me.
But I'm saying it was surprise which I I learned that yeah.
No.
This is and this is all of us.
I mean, when you're sick, your sickness is the most important.
Once you are healthy, you you can just Yeah.
Have other problems.
Right?
Outro & Resources
Scott BennerYeah.
Well, it's nice that they don't have to worry about it anymore.
Who you know, you you can't control what happens next.
Yeah.
I will say this.
This was fantastic.
If the people from Eladon are listening, and I'm sure you are, I would love to interview you too.
And if you ever wanna come back or you have new news, you are you're welcome back here anytime.
You please just let me know.
Piotr Witkowski, MD, PhDThank you very much.
I really appreciate it.
Scott BennerAbsolutely.
I
Piotr Witkowski, MD, PhDappreciate be opportunity to meet again with something exciting to share.
Scott BennerYeah.
Will you be at ADA?
Piotr Witkowski, MD, PhDYes.
I think I was invited to give it to update on on the study.
Yes.
Scott BennerI'm gonna find you and say hello.
I'll be there.
Piotr Witkowski, MD, PhDYeah.
Let's let's let's meet.
Scott BennerThat would be lovely.
Lovely.
Absolutely.
Okay.
Go ahead.
I'm sure you have a thousand things you haven't been doing while you were talking to me.
Piotr Witkowski, MD, PhDThank you.
Scott BennerThank you
Piotr Witkowski, MD, PhDvery much.
Scott BennerTake care.
Having an easy to use and accurate blood glucose meter is just one click away.
Contournext.com/juicebox.
That's right.
Today's episode is sponsored by the Contour NextGen blood glucose meter.
I'd like to remind you again about the MiniMed seven eighty g automated insulin delivery system, which of course anticipates, adjusts, and corrects every five minutes twenty four seven.
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The Juice Box community knows the importance of using technology to simplify managing diabetes.
To learn more about how you can spend less time and effort managing your diabetes, visit my link, medtronicdiabetes.com/juicebox.
Okay.
Well, here we are at the end of the episode.
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Thank you.
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When I created the defining diabetes series, I pictured a dictionary in my mind to help you understand key terms that shape type one diabetes management.
Along with Jenny Smith, who, of course, is an experienced diabetes educator, we break down concepts like basal, time and range, insulin on board, and much more.
This series must have 70 short episodes in it.
We have to take the jargon out of the jargon so that you can focus on what really matters, living confidently and staying healthy.
You can't do these things if you don't know what they mean.
Go get your diabetes defined.
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Go up in the menu and click on series.
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Listen.
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I hired Rob at wrongwayrecording.com.
