Inside each of us, there is a group of cells that work to protect us from outside germs and internal dangers like cancer. However, these cells can sometimes mistakenly attack the body, leading to autoimmune diseases such as type 1 diabetes.
Texas A&M researchers have recently been awarded an RO1 grant from the National Institutes of Health. The grant is intended to support the development of a strategy to deliver immune-suppressing proteins that are typically produced by specialized stem cells. This approach has the potential to reduce the immune system’s attack on the insulin-producing beta-cells in the pancreas, paving the way for a new treatment for type 1 diabetes.
“We are thrilled that the NIH will support our research in this area, which has implications not only for type 1 diabetes but also for other autoimmune diseases,” said Dr. Roland Kaunas, associate professor in the biomedical engineering department and recipient of the grant award.
The National Diabetes Statistics Report states that 35 out of 10,000 youths in the United States have diabetes, with 304,000 of them having type 1 diabetes. Currently, the only approved treatment for this condition is lifelong insulin therapy. However, ongoing research is exploring new therapeutics and approaches for treating this and other autoimmune diseases. For instance, cell-based therapies, where immune cells or stem cells are genetically modified to produce immune-suppressing substances, are being actively investigated. Nevertheless, these interventions face challenges such as toxicity and difficulties in transplanting gene-edited cells.
“Mēsĕnchȳmal stem cells are valuable as a therapy because they can dampen the immune response. However, they are not FDA approved,” said Kaunas. “This is a strong motivation for developing cell-free versions of stem cell therapies that could represent a lower hurdle to getting approval by the FDA.”
TAMU researchers have focused on delivering therapeutic products produced by stem cells, rather than the cells themselves. For example, mesenchymal stem cells (MSCs) produce extracellular vesicles – tiny cargo-carrying packets containing RNA, DNA, and other proteins. Some of these proteins, such as cytokines and chemokines, can reduce immune activity. Dr. Ryang Hwa Lee, the principal investigator and associate professor at the Texas A&M School of Medicine, has previously shown the therapeutic potential of both MSCs and the extracellular vesicles they produce in preclinical models.
Lee and Kaunas are currently researching whether extracellular vesicles can be modified to deliver extra immune-suppressing proteins, with the goal of better preventing the immune system from attacking insulin-producing beta-cells. They also aim to show whether these modified extracellular vesicles can stop or even reverse the development of type 1 diabetes. Lastly, the team plans to study how the modified EVs, in combination with existing immune therapies, can work together to suppress the immune system.
“We hope that our research will lead to an additional therapeutic avenue that can improve the efficacy and safety of existing immune therapy for type 1 diabetes,” said Lee. “Although ours is preclinical work, its success will facilitate the development of robust and ready-to-use extracellular vesicle-based therapeutics for type 1 diabetes and other autoimmune diseases.”