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Podcast: Reducing Inflammatory Response to Transplant

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Transcript of Interview with Norma Sue Kenyon, Ph.D.

The Diabetes Research Institute presents a series of reports on the latest progress in cure-focused research – promising discoveries aimed at restoring natural insulin production in those living with diabetes.

When you get a splinter in your finger ... the skin around it usually turns red ... becomes inflamed. That’s your immune system at work – trying to protect you from germs that could enter your body.

That response – the inflammation – also happens when insulin-producing islet cells are placed in a patient with type 1 diabetes.

The problem: inflammation can shorten the life of the islet cells.

So, scientists at the Diabetes Research Institute are trying to find ways to reduce the inflammatory response – an effort led by Dr. Norma Kenyon.

It’s clear that if you can limit inflammation, you can enhance engraftment and get better long term survival, because all that inflammation enhances and augments the rejection response.

That’s because on the surface of each islet cell are molecules. They stimulate the body’s immune response.

So, scientists at the DRI are trying to block those pathways – stopping those molecules from signaling the immune system.

Kenyon says they’re making progress – but are not there yet.

“We have preliminary studies that show, with three different agents, that limiting inflammation enhances engraftment and long-term graft survival, but we haven’t hit the home run yet, so we see incremental improvement, but not a big change.”

The benefits of this research could be significant. Today, scientists use a large number of islets for each transplant, because they know many cells will die early. If they can reduce inflammation, and more islets survive, they could use fewer cells for each patient. That would increase the supply for others.

Inflammation is only one area of focus for Dr. Kenyon and her team.

It’s part of an overall effort to determine when, and why, transplanted islets begin to lose function over time … and to identify the markers that will tell scientists when it’s happening.

And, she’s trying to determine if islets lose function because of rejection, or a recurrence of the autoimmune attack that created diabetes in the first place – or both.

“If we can understand what is actually happening, rejection, recurrent autoimmunity, and confirm that that’s what happening, then ultimately when we have the right agents, when we have the right therapies, we can tailor the therapy to match whatever the response is.”

Currently, if a patient who received a kidney transplant begins to reject that organ, doctors can tell while that’s happening. They can run tests that show it.

That’s not so with islet transplants.

“There’s no biochemical marker that we can follow that tells us early enough that the body’s beginning to reject the transplant.”

So Kenyon and her team have developed a new way to predict rejection.

They believe they’re beginning to understand how to track the immune system’s cells…as they move towards the transplant site to attack.

At first, she says, an elevated number of these cells can be found in the blood.

“And then prior to the onset of clinical symptoms of rejection, you don’t see them in the blood anymore because they’re at the transplant doing their dirty work.”

Then, after the loss of islets, scientists see the cells back in the blood.

“So we think that cells get activated, they migrate through the blood to the transplant site. During the migration phase we can detect them. But during the actual rejection phase you don’t see them.”

Kenyon says the DRI’s research is still preliminary, and must be validated with other studies. But…

“I’m more convinced than ever that not only will this allow us to determine if a patient is about to reject, but that we can also distinguish between rejection and recurrent type 1 diabetes.”

Kenyon says the DRI is also learning when patients are most likely to reject.

Right now, when patients receive islets, they’re given anti-rejection drugs, also called immunosuppressants. Initially – at the time of the transplant and right after -- they’re given a high dose.

“And what we often see is that as they taper the drugs from the high level to what we call the maintenance level, seven out of the eight patients we were studying actually started to show evidence of rejection and ultimately did lose some graft function as a result of the tapering process. We also see very, very clearly that if you go too low that you’re going to reject.”

As the DRI urgently works toward a cure, Kenyon’s research could be an important piece of the puzzle. At this Institute, she says, she’s knows she’s not alone.

“The DRI continues to be the only place that I am aware of anywhere in the world that has every level of research needed to ultimately achieve a cure. This is the only place I know that has every piece of the puzzle in place. Working together, focusing on teamwork to achieve a cure.”

This has been a production of the Diabetes Research Institute Foundation.

For more information, or to show your support for the Diabetes Research Institute, call 1-800-321-3437.

You also may donate online at


Diabetes Research Institute Foundation
200 S. Park Road, Suite 100
Hollywood, FL 33021
[P]   (954) 964-4040
[TF] (800) 321-3437
[F]   (954) 964-7036

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