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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 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 manage blood sugar levels.
Aiming to prevent the disease - which affects around 1.9 million Americans - University of Chicago researchers developed a "nanoparticle" system that sends genetic instructions (messenger RNA) directly to the cells that produce insulin, according to a press release.
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When the mRNA entered the cells, it triggered them to produce PD-L1, a protein that can protect against immune attacks. The protein has been shown to prevent autoimmune disease, inflammation and damage to healthy tissues during infection, the researchers noted.
In early animal testing, the nanoparticles reached the target cells and triggered the protective effect. The approach was also shown to be effective in animal models where human beta cells were transplanted into mice, the release stated.
The findings were published in the journal Cell Reports Medicine.
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"In this initial therapeutic proof of concept, we showed that we were able to deliver PD-L1 mRNA with our nanoparticle system, enable a delay in type 1 diabetes progression in mice, and also show potential translational relevance within human cells," said lead study author Jacob Enriquez, Ph.D., a postdoctoral scholar at UChicago, 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've also shown that they can produce PD-L1 for immune protection."
The study's main limitation was that it was conducted in laboratory and animal models and not in humans. It also did not explore long-term safety implications or how long the protection lasted.
Further testing is needed to confirm safety, dosing and effectiveness before human trials, the researchers noted.
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 stated. Current prevention strategies often involve broadly modifying the immune system to slow the autoimmune attack on insulin-producing cells.
"This is generating a new level of excitement, because now we're thinking about engineering beta cells with the knowledge we've accumulated over the years," said co-author Raghu G. Mirmira, who is also director of the UChicago Diabetes Research and Training Center.
"Going forward, it's 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.
