An NCI-designated Comprehensive Cancer Center
By Wayne Lewis | November 1, 2019
Bart Reop in laboratory Bart Roep, Ph.D.
Type 1 diabetes has long been thought of as an error of the immune system in which the body’s defenses misidentify insulin-producing beta cells — found in structures of the pancreas called “islets” — as foreign or defective. But a landmark 2017 study led by Bart Roep, Ph.D., holder of City of Hope’s Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes, has turned that idea on its head.
We sought to debunk some of the misconceptions about the disease in a conversation with Roep, who also serves as director of The Wanek Family Project for Type 1 Diabetes and as professor and founding chair of the Department of Diabetes Immunology.
How did your 2017 findings change how you thought about type 1 diabetes?
I used to say that diabetes is a mistake of the immune system and now I’m actually saying, “No, it’s a mistake of the beta cells.”
There are these changes that are incurred by stress, and the immune system tries to clean up. They’re the same changes that you also see in cancers. So it’s actually with good intentions that the immune system starts to respond to the distressed islets.
How does that influence your approach to developing new treatments?
If you can make beta cells resilient and happy, so they are not subject to these well-intended immune responses, that’s when you take the fuel away from the fire.
What we do now at City of Hope — which is unique in the whole therapy field — is that we realize that we will not be able to cure a patient with immunotherapy alone. We must revive and revitalize the pancreatic beta cells.
How else has the understanding of type 1 diabetes changed in recent years?
Not so long ago when I was doing post-academic training of physicians, I had a slide titled, “Everything that I Learned in Medical School on Type 1 Diabetes Is Wrong.”
It starts with the genetics. Type 1 diabetes is not an inherited disease. At best, you can inherit an increased genetic risk for the disease. Basically, the risk genes for diabetes are the winners of the Middle Ages. They are the survivors of the plagues and epidemics. And they actually endow the carriers of those genes with the best immune system.
Another one is, we thought that it’s a children’s disease. That turns out to be wrong. We used to think 80% of patients get diabetes before the age of 18, and now we think it’s less than 50%. That means that most of type 1 diabetes occurs in adults. And that makes it more difficult to distinguish from type 2 diabetes, which used to be called “adult-onset diabetes.”
And then, we thought it was antibodies at the root of the disease. They’re not. It’s the T cells in the immune system that are responsible for the destruction. But they’re also responsible for regulating the immune response, so these T cells give you ways to potentially cure the disease.
What you’ll see in textbook medicine is that the diagnosis is the end game in type 1 diabetes, since virtually all the islets have been destroyed and there’s no insulin. That’s not true. At best, 50% is gone. So now we try to preserve those beta cells and get them back in action.
And finally, the most important one people say is that type 1 diabetes cannot be cured. But yes, it can be cured. Even if it is only a few patients so far, the proof is there, even from my own work, that you can cure people with type 1 diabetes.
What do we mean when we say “cure”?
With the different forms the disease takes, there will not be a magic bullet. There will not be a single therapy that can treat everybody in the same way.
A few years ago, we raised eyebrows. Some were unhappy with our claim that we want to cure type 1 diabetes in six years. These days, when people ask, “Is it true that you want to cure diabetes in six years?” I say, “Well no, that’s a misunderstanding. I want to cure diabetes today.”
It reflects our sense of urgency. We cannot wait. It has taken too long since the discovery of insulin, and now we enter a new chapter where we go from dealing with the symptoms, coping with high blood sugar, to actually starting to treat the cause. This is an exciting time for everybody — us, but also the patients.
For some, stopping disease progression, halting the immune attack on beta cells and preserving some insulin production is a cure. For others, it is preventing diabetic complications that patients fear most. The goal of no longer injecting insulin is something that we ultimately strive for, but that’s a very high bar. I fear that we will only be able to achieve that in a small number of patients, but it can be done. That we have shown. So let’s not give up. Let’s keep our hope, which is of course the keyword of our institute.
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