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Viral Gene Therapy

Could Reprogramming Cells Help Treat Type 1 Diabetes?

More than 300 million people around the world are living with diabetes. Currently, there is no cure, but scientists are continually researching and testing different methods for treating and managing this disease. One of the major obstacles faced in treating type 1 diabetes is that the body’s immune system attacks and destroys insulin-producing beta cells, whether these cells are naturally occurring or introduced through medical treatment.

Some researchers are looking at ways to reprogram the body’s own cells to function as insulin-producing cells to help better control blood sugar. The human pancreas contains small niches where hormone-making cells reside. Within these niches, two different cells predominate: alpha cells, which make glucagon, and beta cells, which make insulin. In individuals with type 1 diabetes, insulin-producing cells are destroyed, but glucagon cells are not.

Scientists developed a method using viruses as carriers to deliver two genes that are present in insulin but glucagon cells to the glucagon cells allowing the cells to be able to produce insulin. Glucagon cells are a good option for this process because they are similar to insulin cells and appear in abundance in islets within the pancreas already. A decrease in these cells as they were reprogrammed did not appear to affect glucose metabolism.

These experiments have been performed in NOD mice, which are mice that develop diabetes very close to human diabetes. Following the experiment, the diabetes disease appeared to have resolved in the diabetic NOD mice thanks to the new source of cells making insulin in their pancreas. However, human application of this technique will take time since targeting specific cells is complicated, and the use of viral elements creates side effects that need to be resolved.

It is this type of research and these experiments that lead to breakthroughs in the treatment, management, prevention, and improvement in the quality of life for individuals living with type 1 diabetes. Though not involved in this particular study, the Diabetes Research Connection supports early-career scientists through funding for novel research on type 1 diabetes. Learn more about current projects and support their advancement by visiting http://diabetesresearchconnection.org.

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Role of the integrated stress response in type 1 diabetes pathogenesis
In individuals with type 1 diabetes (T1D), the insulin-producing beta cells are spontaneously destroyed by their own immune system. The trigger that provokes the immune system to destroy the beta cells is unknown. However, accumulating evidence suggest that signals are perhaps first sent out by the stressed beta cells that eventually attracts the immune cells. Stressed cells adapt different stress mitigation systems as an adaptive response. However, when these adaptive responses go awry, it results in cell death. One of the stress response mechanisms, namely the integrated stress response (ISR) is activated under a variety of stressful stimuli to promote cell survival. However, when ISR is chronically activated, it can be damaging to the cells and can lead to cell death. The role of the ISR in the context of T1D is unknown. Therefore, in this DRC funded study, we propose to study the ISR in the beta cells to determine its role in propagating T1D.
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Taming a Particularly Lethal Category of Cells May Reduce/Eliminate the Onset of T1D
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