Research led by City of Hope’s Bart O. Roep, Ph.D., advances personalized medicine for children with type 1 diabetesNovember 22, 2019
Novel ways to classify patients for better treatment outcomes published in Diabetologia and Diabetes Care
DUARTE, Calif. — As science continues to advance understanding 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.
Led by Bart O. 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, a new study characterizes how immune responses to type 1 diabetes (T1D) differ among individuals much more than previously thought. The study characterizes those differences in children with T1D, which represents an important first step toward personalized medicine for this patient population.
Published in Diabetologia, the journal of the European Association for the Study of Diabetes, Roep and his colleagues found that children with T1D do differ in their islet autoimmune signatures, or how they respond to immune intervention therapies. But rather than many shades of grey, 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.
T1D 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.
“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/will require different intervention therapies.”
“Indeed, we already know that children not showing much islet autoimmunity will have a great prospect for complete remission of T1D after autologous bone marrow transplantation,” he said. “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 give 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 T1D, 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” and 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,” Roep said. “It’s the realization that no magic bullet will cure all, so precision medicine must be tailored to the individual. Our recent findings highlighted in the Diabetologia paper provide the tools for the fine-tuned diagnosis of T1D to allow for selecting the right patients for the right therapeutic immune intervention strategy.”
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About City of HopeCity of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is the highest ranked cancer hospital in the West, according to U.S. News & World Report’s Best Hospitals: Specialty Ranking. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.