Healthcare (Commonwealth Union) – Scientific advances made in one illness do not always translate to breakthroughs in others. However, that has been an unexpected path for a research team at the Mayo Clinic. After discovering a sugar molecule that cancer cells display on their surfaces to evade detection by the immune system, the scientists realized that this same molecule might eventually be useful in treating type 1 diabetes, previously called juvenile diabetes.
Type 1 diabetes is a long-lasting autoimmune disorder where the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. This condition, is influenced by genetic and other factors. As Type 1 diabetes accounts for 5-10% of all cases of diabetes, finding new and effective ways of its treatment is key.
In the research conducted by the Mayo Clinic, the team reversed a mechanism typically seen in cancer. Cancer cells avoid immune attack through various strategies, including cloaking themselves with a sugar called sialic acid. The investigators demonstrated in a preclinical diabetes model that coating beta cells with this sugar molecule can help the immune system accept these cells rather than destroy them.
Immunologist Virginia Shapiro, Ph.D., the lead author, of the study that was published in the Journal of Clinical Investigation indicated that their results show that it is feasible to modify beta cells so they no longer trigger an immune reaction.
A few years back, Dr. Shapiro’s group showed that an enzyme called ST8Sia6, which increases the amount of sialic acid on the surface of tumor cells, helps these cells disguise themselves so they don’t appear as foreign targets to the immune system.
“This enzyme essentially ‘sugar coats’ cancer cells, shielding them from a typical immune attack. We wondered whether the same enzyme could also protect normal cells from an abnormal immune response,” explains Dr. Shapiro. The team initially demonstrated this concept using a lab-created model of diabetes.
In their current research, the group studied preclinical models that naturally develop autoimmune (type 1) diabetes, closely mimicking the disease progression seen in humans. They engineered beta cells in these models for the production of the ST8Sia6 enzyme.
The results showed that these engineered beta cells were about 90% successful in preventing the onset of type 1 diabetes. Normally, these beta cells are destroyed by the immune system in type 1 diabetes, but in this case, they were preserved.
Importantly, the researchers discovered that the immune reaction to the engineered cells seems to be very precise, according to M.D.-Ph.D. student Justin Choe, the study’s lead author. Choe carried out this research as part of the Ph.D. portion of his dual degree program at the Mayo Clinic Graduate School of Biomedical Sciences and the Mayo Clinic Alix School of Medicine.
“Though the beta cells were spared, the immune system remained intact,” explained Choe. The scientists had the ability to see active B- and T-cells and proof of an autoimmune response against another disease procedure. “We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes.”
There is currently no cure for type 1 diabetes. Treatment typically involves administering synthetic insulin to control blood sugar levels, or for some patients, receiving a transplant of pancreatic islet cells that contain the essential beta cells. Since transplantation requires suppressing the entire immune system, Dr. Shapiro is investigating the use of engineered beta cells within transplantable islet cells to potentially enhance treatment options for patients.
“A goal would be to provide transplantable cells without the need for immunosuppression,” added Dr. Shapiro. “Though we’re still in the early stages, this study may be one step toward improving care.”
