A modern approach to treating—and potentially curing—type 1 diabetes (T1D) is underway at the Medical University of South Carolina (MUSC), fueled by a $1 million grant from Breakthrough T1D. Researchers are aiming to reimagine how the immune system interacts with the pancreas, offering a beacon of hope for the 1.5 million Americans currently living with the autoimmune condition, according to the Centers for Disease Control, and Prevention. This innovative strategy combines stem cell biology, immunology, and transplantation science, with the ambitious goal of restoring insulin production without the need for lifelong immunosuppressive drugs.
The project, led by Leonardo Ferreira, Ph.D., assistant professor of Pharmacology and Immunology at MUSC, centers on “reprogramming immunity” to address the root causes of T1D. “These awards support the most promising perform that can significantly advance the path to cures for type 1 diabetes,” said Ferreira. “This is what Breakthrough T1D believes is the next wave in type 1 diabetes therapy.” The research builds on a 2021 Discovery Pilot grant from the South Carolina Clinical & Translational Research Institute (SCTR), which initially connected Ferreira with collaborator Holger Russ, Ph.D.
Engineering the Immune System for Beta Cell Protection
Type 1 diabetes arises when the body’s immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. Current treatment relies on careful blood glucose monitoring and insulin injections. Ferreira’s team is taking a novel approach: engineering the immune system itself to protect these vital cells. They specialize in modifying immune cells using chimeric antigen receptors, or CARs, which act like guided missiles, directing regulatory T cells (Tregs) to specific targets.
Tregs are crucial for maintaining immune balance, preventing the immune system from overreacting and causing autoimmune damage. In T1D, Tregs are often unable to effectively control the attack on beta cells. By equipping Tregs with CARs that recognize a specific protein on beta cells, the researchers aim to create a targeted defense system. This “lock and key” interaction signals the immune system to stand down, preserving insulin production.
Addressing the Challenges of Islet Cell Transplants
Islet cell transplants, which involve transferring beta cells from a donor pancreas, can restore insulin production in some individuals with T1D. However, this approach faces two major hurdles: a shortage of donor tissue and the risk of immune rejection. To overcome the donor shortage, Ferreira and his team are producing stem cell-derived islet cells in the laboratory. This offers the potential for a virtually unlimited supply of cells for research and future clinical use.
The immune rejection problem is being tackled head-on with the engineered Tregs. Transplanted cells, like any foreign tissue, can trigger an immune response. The modified Tregs act as “bodyguards,” protecting the transplanted beta cells from attack. Crucially, this strategy aims to eliminate the need for long-term immunosuppressive drugs, which carry significant risks, particularly for children.
A Collaborative Effort
Ferreira is collaborating with two leading experts in their respective fields. Holger Russ, Ph.D., associate professor of Pharmacology and Therapeutics at the University of Florida, is a leader in stem cell research for T1D. Michael Brehm, Ph.D., of the University of Massachusetts Medical School, specializes in developing humanized mouse models, which allow researchers to study human immune responses in a controlled setting. This collaborative approach brings together diverse expertise to tackle the complexities of T1D.
The Potential for an “Off-the-Shelf” Therapy
The ultimate goal is to develop an “off-the-shelf” therapy combining engineered Tregs and lab-grown beta cells. This would allow for widespread distribution and administration through transplantation. “We’re trying to develop a therapy that would work for all people with type 1 diabetes at every stage, even people who have had the disease for many years and have no beta cells left,” Ferreira explained.
Looking Ahead: Durability and Long-Term Impact
While preclinical studies using humanized mice have shown promising results, with protective effects lasting up to one month, further research is needed to determine the long-term durability of this therapy. The new funding will support investigations into extending this protection, optimizing delivery methods, and exploring the potential of multiple doses. Researchers are also focused on understanding how this approach might benefit individuals at different stages of the disease.
The implications of this research extend beyond diabetes. Success could represent a major advance in regenerative medicine and immune-based therapies, potentially paving the way for treatments for other autoimmune diseases. Ferreira believes this work could fundamentally change how medicine is practiced, shifting the focus from managing symptoms to replacing missing cells and understanding the underlying causes of disease.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
The team plans to continue refining the therapy and conducting further preclinical studies before moving towards clinical trials. Updates on the research will be available through the Medical University of South Carolina and Breakthrough T1D. Share your thoughts and experiences with type 1 diabetes in the comments below.
