Innovative approach to diabetes could protect cells and prevent disease

Researchers have developed an mRNA therapy that could help prevent or slow the development of type 1 diabetes.

With this chronic autoimmune disease, the body’s immune system attacks and destroys the insulin-producing beta cells in the pancreas, according to the American Diabetes Association. People with type 1 diabetes must take insulin daily to survive and control blood sugar levels.

Aiming to prevent the disease, which affects about 1.9 million Americans, researchers at the University of Chicago developed a “nanoparticle” system that delivers genetic instructions (messenger RNA) directly to cells that produce insulin, according to a news release.

When the mRNA entered the cells, it prompted them to produce PD-L1, a protein that can protect against immune attacks. The protein has been shown to prevent autoimmune diseases, inflammation and damage to healthy tissues during infection, the researchers noted.

In the first animal tests, the nanoparticles reached the target cells and triggered the protective effect. The approach also proved effective in animal models in which human beta cells were transplanted into mice, according to the release.

The findings were published in the journal Cell Reports Medicine.

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“In this initial therapeutic proof of concept, we demonstrated that we were able to deliver PD-L1 mRNA with our nanoparticle system, enable a delay in the progression of type 1 diabetes in mice, and also show potential translational relevance within human cells,” the study’s senior author, Jacob Enriquez, Ph.D., a postdoctoral scholar at UChicago, said in the release.

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“So not only have we provided a vehicle for delivery to beta cells, which is innovative and exciting, but we have also shown that they can produce PD-L1 for immune protection.”

The main limitation of the study was that it was carried out in the laboratory and in animal models and not in humans. It also did not explore the long-term security implications or how long the protection lasted.

More testing is needed to confirm safety, dosage and effectiveness before human trials, the researchers noted.

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If future human studies confirm these findings, the approach could serve as a new way to prevent or delay type 1 diabetes by protecting insulin-producing cells, the researchers said. Current prevention strategies often involve extensively modifying the immune system to curb the autoimmune attack on insulin-producing cells.

“This is generating a new level of excitement, because we are now thinking about engineering beta cells with the knowledge we have accumulated over the years,” said co-author Raghu G. Mirmira, who is also director of the Diabetes Research and Training Center at the University of Chicago.

“Looking ahead, it is a promising tool because we can target a specific cell type without harming other cells.”

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The study received funding from Breakthrough T1D and the National Institutes of Health.