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‘Eureka moment’
April 2017
EDIT CONNECT
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DUARTE, Calif.—About 1.5 million Americans suffer from type 1 diabetes (T1D), previously known as juvenile diabetes, which results from
the loss of insulin-producing cells in the pancreas. While the root cause of T1D was believed to be the immune system mistakenly identifying those insulin-
secreting beta cells as a potential danger and, in turn, destroying them, an international team of researchers has found a mechanism in which stressed beta
cells are actually causing the immune response that leads to T1D.
City of Hope’s Dr. Bart Roep, the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and professor/founding chair of the
Department of Diabetes Immunology, along with researchers from the Leiden University Medical Center in the Netherlands, reported the results in the journal Nature Medicine. The work was supported by the Dutch Diabetes Research Foundation, the DON Foundation and the JDRF.
Roep said, “Ever since I started studying medicine, I
was frustrated that we deal with the consequences, not the cause, of T1D. Now that we can identify the cause, we can address it with new types of
therapies.”
Roep, who is director of The Wanek Family Project for Type 1 Diabetes, added, “Our
findings show that type 1 diabetes results from a mistake of the beta cell, not a mistake of the immune system. The immune system does what it is supposed to
do, which is respond to distressed or ‘unhappy’ tissue, as it would in infection or cancer. The mistake is in the beta cells, the most
hardworking cells in the body.”
Roep said he had an epiphany about this three years ago—“one of
those rare eureka moments in an area where one has to be prepared for disappointments.” He began to pursue it when he relocated to the City of Hope, an
independent research and treatment center for cancer, diabetes and other life-threatening diseases. Not only is the City of Hope one of only 47 comprehensive
cancer centers, the highest recognition bestowed by the National Cancer Institute, it is also a pioneer in the use of recombinant insulin, Roep noted.
In order to gain a better understanding of why the immune system attacks the body’s own source of
insulin—the pancreatic beta cells in the islets of Langerhans—the team took some clues from cancer molecules that are targeted by the immune
system after successful treatment of the cancer with immunotherapy. One such target is a so-called nonsense protein, which results from a misreading of a DNA
sequence that makes a nonfunctional protein. Because the same type of protein error is also produced by the beta cells in T1D, Roep’s team believes
that a “wrong read” of the insulin gene itself proves to be a major target of the immune system. This error product of the insulin gene is made
when beta cells are stressed, Roep explained.
“Our study links antitumor immunity to islet autoimmunity, and
may explain why some cancer patients develop type 1 diabetes after successful immunotherapy,” he added. “This is an incredible step forward in
our commitment to cure this disease.”
As the paper, titled “Autoimmunity against a defective ribosomal
insulin gene product in type 1 diabetes,” explains, the findings “further support the emerging concept that beta cells are destroyed in T1D by a
mechanism comparable to classical antitumor responses where the immune system has been trained to survey dysfunctional cells in which errors have
accumulated.”
“Now we can reread the RNA and create great antigens,” Roep said. He explained
that the results of the study are giving him new insight for his work in developing new vaccines to desensitize the immune system so that it will tolerate
islets again, as well as for research into combining immunotherapy with more traditional diabetes treatments to reinvigorate islets, adding, “We can
take away the fuel of the immune response by making the beta cells happy, create new drugs that affect the beta cells and create new proteins.”
Roep described cancer and diabetes as “two sides of the same coin,” in which the body is producing too much
or too little immune response. While immunotherapy is “a big breakthrough in cancer treatment,” some patients who are cured of cancer develop
T1D, he said. “The window between cancer and diabetes could be the time to tweak the immune system and avoid the problem.”
“Some of the drugs that help with insulin production can help to relax the beta cells, even before the clinical
manifestation of the disease,” he concluded.
Code: E041702 Back |
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