An NCI-designated Comprehensive Cancer Center
By Letisia Marquez | January 16, 2017
Wanek Project - Bart Roep Bart Roep, Ph.D.

Diabetes affects over 422 million people worldwide according to the World Health Organization, but no two patients are alike. So in 2017 and beyond, treatments will increasingly make use of precision medicine to personalize treatment options. At City of Hope, researchers are using a transformative gift to speed these treatments to patients.

On January 16, the Wanek family bestowed City of Hope’s Diabetes and Metabolism Research Institute with a significant contribution to support the institution’s goal of curing type 1 diabetes (T1D) in six years and create The Wanek Family Project for Type 1 Diabetes. The gift follows on the heels of an alliance between City of Hope and the Translational Genomics Research Institute (TGen), an organization that applies genomic analysis and bioinformatics in the development of personalized approach to therapies for diseases like cancer and diabetes.

“One of the lessons we’ve had recently is that every patient is different,” said Bart Roep, M.D., Ph.D., director of the Wanek Family Project. “So you really have to do a fine diagnosis, like we do in cancer, to offer the best type of therapy to the individual patient — something we call personalized medicine, or precision medicine.”

But for that, he says, researchers first need to understand what makes one T1D patient different from another. They also need to understand the mechanisms behind how the immune system mistakenly destroys beta cells — the cells that make insulin — to cause T1D.

“That is what the Wanek Family Program entails, and we’re taking it from different angles,” said Roep, who is also the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and Professor and founding Chair, Department of Diabetes Immunology at City of Hope.

We have people here that are experts in beta cell function. We have people that are experts in the complications of diabetes, which of course we’re trying to prevent. And we think we are experts in the immune processes that cause type 1 diabetes and the genetic associations of that. So collectively we have all the different disciplines that are required to build a program that can cure type 1 diabetes." Bart Roep, Ph.D.

Personalized Care

But until there is a cure, Fouad Kandeel, M.D., Ph.D., professor and chair of the Department of Clinical Diabetes, Endocrinology & Metabolism, says that the “use of personalized strategies for patient management will avoid the practice of one-size-fits-all therapies which frequently result in unintended side effects.”

Wanek Project - Fouad Kandeel Fouad Kandeel, M.D., Ph.D.

For example, he points to the fact that the use of immunosuppressant drugs for the support of islet cell transplantation — a technique that replaces islet cells destroyed by T1D with healthy ones — can be associated with increased risk of infections and cancer.

“But, with the use of biological immune modifiers that can specifically target just the immune mechanisms directed at damaging transplanted islets, we may be able to support transplantation without the collateral damage to other immune system functions,” said Kandeel, who is also chair of the Department of Translational Research and Cellular Therapeutics, director of the Islet Cell Transplant Program and associate director of the Diabetes & Metabolism Research Institute..

“Rather than suppressing the immune system, we’ll negotiate with it,” added Roep, who says this attitude guides much of the diabetes work at City of Hope. “It’s using a velvet glove approach instead of giant hammer against the disease.”

A 'Bold Approach'

Advancement in the use of artificial pancreas systems — technology that monitors and automates blood-sugar management in the body — is also expected in the coming years, said Kandeel, along with more results from multi-center clinical trials using non-insulin hypoglycemic agents to aid in the management of both T1D and type 2 diabetes (T2D). These insights, in addition to the availability of a wide range of such hypoglycemic agents, will likely yield more personalized ways of managing T2D as well.

In addition, he expects to see more clarification and understanding of the precise mechanisms associated with beta cell management of the insulin-producing cells that are damaged in T1D and T2D, something that Debbie Thurmond, Ph.D., professor and founding Chair, Department of Molecular & Cellular Endocrinology and the Ruth B. & Robert K. Lanman Chair in Gene Regulation and Drug Discovery Research.

Wanek Project - Debbie Thurmond Debbie Thurmond, Ph.D.

Both T1D and T2D develop due to dysfunction and demise of the insulin-secreting beta cells, but T2D has the additional defect of “insulin resistance" in the skeletal muscle, a condition where the muscle no longer responds to a normal level of insulin.  

“Our Wanek Family Project studies will derive new innovations to fix the beta cell dysfunction that will benefit type 1 diabetes, which will in turn benefit type 2 patients, too,” said Thurmond, who is also founding Chair of the Department of Molecular & Cellular Endocrinology. “The targets that we are focusing on also hold promise as skeletal muscle insulin sensitizing drugs, such that a type 2 diabetes patient will take one drug to effectively treat both the islets and the muscle concurrently, to remediate the disease. In this bold approach, my team is devising an immunotherapy approach to replenish function to both tissues, simultaneously, by over-riding the dysfunctional processes.”

She and her team have published in elite journals the proof of concept for this in animal models, and are now working with human tissues in preparation for going into clinical trials within the next three years.

Breakthroughs in Immunotherapy

“City of Hope is a place where we know how to do immunotherapy,” said Roep. “This has been the breakthrough in cancer therapy. And my dream and ambition is to do the very same thing for type 1 diabetes. One of the things I’m very keen to do is learn from the cancer experts what to do in type 1 diabetes. In cancer, precision medicine, personalized medicine, has been in vogue for years and in diabetes we’re just starting to learn that the disease is much more diverse than we anticipated. So that means that it will not be a magic bullet. We have to be prepared for the right therapies and design those and tailor them to the individual needs of the patient.”

He says that thanks to the Wanek Family Project, City of Hope researchers have a whole range of clinical trials that they’re conducting using cell therapy. Cell therapy, says Roep, has particular demands — not every institute can do it.

“In fact only very few institutes can do it,” he said. “And City of Hope happens to be one of those places where we have experience doing thousands and thousands of cell therapies. That’s one of the reasons why I felt attracted to join the forces with the City of Hope and run this program here.

“Plus City of Hope has a 'sense of urgency' as one of its mottos and I agree with that,” continued Roep. “If you say you want to cure a disease, you know you better be prepared. And I think we are prepared here.”


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