Immunologist Bart Roep, Ph.D., Thinks T1D Cure Is in Sight

June 27, 2017 | by Samantha Bonar

Bart Roep in lab Bart O. Roep, Ph.D.
Bart O. Roep, Ph.D., has dedicated his life to the search for a cure for type 1 diabetes. And he thinks he is on the brink.
 
Roep, an internationally renowned immunologist who joined City of Hope last year from the Netherlands’ Leiden University Medical Center, was recently named the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes. He believes that this endowment and a $50 million funding project led by the Wanek family will be key in stopping the disease.
 
“We need to do something in addition to treating the symptoms,” Roep said. “Diabetes has surpassed cancer as a cause of death. One of the goals of the diabetes program at City of Hope is to accelerate the progress against the disease. And the new $50-million grant is a catalyst to get there faster.”
 
Instead of dealing with the effects of the disease, Roep is committed to treating the disease itself.
 
“For 100 years, we’ve known how to deal with the symptoms,” he said. “Now, for the first time, we can tackle the cause. This is really one of the most exciting times since the discovery of insulin. We have the opportunity to offer a completely new generation of therapy to these patients.”
 
After studying the mechanism of type 1 diabetes for the last two decades, Roep, the founding chair of the Department of Diabetes Immunology within the Diabetes & Metabolism Research Institute at City of Hope, recently had his “Eureka!” moment when he realized that the disorder varies greatly from patient to patient. 
 
“One of the new insights is that diabetes is very diverse,” he said. Based on that understanding, a key component of Roep’s current research “is to understand the differences in disease between patients, and accordingly tailor the type of immune strategy that we offer them.”
 
Roep explained that type 1 diabetes results from a “mistake” of the immune system. Immune cells that normally protect humans from infections and cancer mistakenly attack the insulin-producing beta cells found in the pancreas, leaving the patient dependent on insulin injections.
 
Previously, it was thought that type 1 diabetics had no beta cells. “Very new data” shows that “the majority of type 1 patients still have some beta cells,” Roep said. However, they are “hiding” or “hibernating” or otherwise just not functioning. 
 
“As long as you still have beta cells, there is a reason to do immunotherapy,” he said. “But there’s a sense of urgency. You need to protect those beta cells. If we can rescue those remaining cells, it can truly mean that you can cure the patient from disease. The new findings make me extremely excited,” he said.
 
In addition, some diabetics have largely genetically based disease. Others’ disease progression may be triggered by chronic inflammation, metabolic stress or even a viral infection. There are multiple differences on a molecular level from patient to patient and each variant requires the appropriate treatment strategy.
 
Traditionally, type 1 was thought of as “juvenile diabetes” and type 2 as adult-onset. “But half of the patients get type 1 diabetes after the age of 30. This is brand new information,” Roep said. Some even have a mix of type 1 and type 2, something that was not considered before, according to Roep. “Unhappy beta cells” is what the types have in common, he said.
 
Because there is no one-size-fits-all disease, “it is quite clear that there won’t be a magic bullet therapy,” Roep said. That’s why immune-profiling is a key part of his program. “We believe that we can read in the blood what variants we see and then we can assign the proper immunotherapy,” he said.
 
Once an individual patient’s disease is better understood, this knowledge can be tailored to personalize immune intervention strategies (including gene therapy, stem cell therapy and bone marrow transplantation) with the ultimate goal of curing the disease. 
 
“That is why it’s so essential that we are taking this multidisciplinary approach,” Roep said. “Genetics, immunology, endocrinology — we need to merge all of these insights into coming up with new treatments.”
 
Novel new treatments underway at City of Hope include a vaccine that is currently in clinical trials in the Netherlands. 
 
“We take immune cells of the patient and treat them outside of the body with vitamin D3 and some other goodies and inject them back into the patient as a way to repair the immune system,” Roep explained. “Rather than trying to suppress the immune system, we’re trying to negotiate with it. We’re going to educate it.”
 
Roep compares this treatment to allergy shots: “Once you know the allergen, you can desensitize the patient to it,” he said. “With diabetes, we think we know the ‘allergen’ that is causing the destruction of the cells that create insulin. We have taken a part of that molecule and are using it in our vaccine.”
 
If they don’t have enough reserves of beta cells to be reactivated through the vaccine, City of Hope offers beta cell transplants from healthy donors.
 
“With the new insight that patients are all different and there is no magic bullet, I am confident that we can cure patients with diabetes,” Roep said. “I am also certain we will not be able to cure everybody. But we have set the bar high. We believe that we can stop the disease — but it is a matter of luck whether we have rescued enough beta cells.
 
“Cure means not just stopping the disease, but making people insulin independent again,” he said. “I think we can make a difference. The time is ripe.”
 
 

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