An NCI-designated Comprehensive Cancer Center
By Katie Neith | November 27, 2019
Bart Roep bio Bart Roep, Ph.D.
As science continues to advance our understanding of how diseases like cancer and diabetes operate in the human body, the models for treatment have increasingly moved away from one-size-fits-all approaches and toward more individualized therapies.
For example, recent studies and clinical evidence have shown that immune responses to type 1 diabetes differ among individuals much more than previously thought. Now, researchers led by Bart Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes at City of Hope and director of The Wanek Family Project for Type 1 Diabetes, have been able to characterize those differences in children with type 1 diabetes, which represents an important first step toward personalized medicine for this patient population.  

Identifying Key Subgroups

Type 1 diabetes results from the destruction of insulin-making beta cells by the body’s own immune system. Treatments rely on protecting cells called islets — which contain the insulin-producing beta cells — from inflammatory attacks, but immune responses vary.
In Roep’s recent study, outlined in the paper “Clinical and genetic correlates of islet-autoimmune signatures in juvenile-onset type 1 diabetes,” published in the journal Diabetologia on November 19, he and his colleagues found that children with type 1 diabetes do differ in their islet autoimmune signatures, or how they respond to immune intervention therapies. But rather than many shades of gray, they only saw three subgroups: children who respond to all islet proteins, those who respond to none, and those who only responding to two or three proteins.
“Because these types of immune responses have genetic correlates, the scientific advance is really the clinical application,” Roep said. “We now have fancy technology to identify variants of type 1 diabetes that may require different intervention therapies.”
“Indeed, we already know that children not showing much islet autoimmunity will have a great prospect for complete remission of type 1 diabetes after autologous bone marrow transplantation,” he continued. “Adults with the same signature will virtually all remit after islet transplantation and become insulin independent, whereas none of the patients responding to the 'full house' of islet proteins will remit after islet transplantation and 90% would have no benefit, or relapse within the first three years after autologous bone marrow transplantation.”
Collectively, the data provided by the study gives new insights into type 1 diabetes disease heterogeneity, or complexity, and highlights the importance of grouping patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalized disease management. 

“We hope to soon be able to select patients for particular immune intervention strategies to offer the right therapy to the right person,” Roep said. “Part of this process will be to engage our affiliate, the Translational Genomics Research Institute, or TGen, to help us refine the genetic signatures, so we may no longer need a variety of tests to measure islet autoimmunity and diagnose disease variants.”

A New Path Forward

Roep is far from alone in thinking that drilling down into patient subgroups represents an important step toward better treatments. In fact, in an effort to bolster work being done to advance personalized medicine for type 1 diabetes, he was also recently part of a group of key thought leaders organized by the National Institutes of Health (NIH) to lay out a detailed plan of action that introduces patients and physicians to a new concept of disease subtypes with different immune signatures like those identified in Roep’s Diabetologia paper.
As part of the NIH’s Diabetes TrialNet Consortium, the diabetes experts came together over two days to explore myriad ways in which patients differ in their response to both the disease and to various treatments. This led to the first proposal of disease variants, or “endotypes” that are characterized by underlying biological mechanisms, which will help to guide future therapies toward personalized or precision medicine.
A paper in Diabetes Care called “Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes,” available now online, gives a roadmap of their proposal through which the field can incorporate the endotype concept into laboratory and clinical practice.
“This approach is just like what happened in cancer and made the field jump forward,” said Roep. “It’s the realization that no magic bullet will cure all, so precision medicine must be tailored to the individual. Our recent findings provide the tools for the fine-tuned diagnosis of type 1 diabetes to allow for selecting the right patients for the right therapeutic immune intervention strategy.”

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