At the Medical University of South Carolina (MUSC), researcher Dr. Leonardo Ferreira is leading an ambitious effort to change the way type 1 diabetes (T1D) is treated. With $1 million in support from Breakthrough T1D, the world’s leading research and advocacy organization, Ferreira and collaborators at partner institutions are testing new strategies aimed at treating and potentially curing the disease.
Their approach integrates stem cell science, immunology, and transplantation research. The central goal is simple but bold. The goal is to restore insulin-producing beta cells in T1D patients without the need for immunosuppressants.
“These awards support the most promising research that has the potential to significantly advance treatments for type 1 diabetes,” Ferreira said. “This is what we believe Breakthrough T1D is the next wave in type 1 diabetes treatment.”
Designing the immune system to protect insulin cells
Mr. Ferreira specializes in modifying the immune system using chimeric antigen receptors (CARs). These engineered receptors help guide regulatory T cells, known as Tregs, to specific targets in the body. Tregs play an important role in keeping the immune response under control and preventing excessive damage, such as the autoimmune attacks seen in T1D. Simply put, they act like bodyguards, preventing your immune system from overworking and harming healthy tissue.
He collaborates with two notable collaborators. Dr. Holger Rath, associate professor of pharmacology and therapeutics at the University of Florida, is a leader in stem cell research in T1D. Many scientists see this field as the future of transplantation, as stem cells can provide a virtually unlimited supply of islet cells for research and clinical use. Dr. Michael Brehm of the University of Massachusetts Medical School completes the team. He is known for developing humanized mouse models that help researchers study human immune and metabolic responses in T1D.
what happens in type 1 diabetes
Type 1 diabetes (T1D) is an autoimmune disease in which the immune system mistakenly attacks insulin-producing beta cells in the pancreas. Without these cells, the body cannot properly regulate blood sugar levels. T1D patients must closely monitor their blood sugar levels and rely on insulin injections to survive. According to the Centers for Disease Control and Prevention, approximately 1.5 million Americans are living with the disease. Over time, it can cause serious complications such as nerve damage, blindness, coma, and even death.
The new Breakthrough T1D award builds on the 2021 Discovery Pilot grant from the South Carolina Clinical Translational Research Institute (SCTR), which first brought Ferreira and Russ together. This initial support has laid the foundation for this large-scale project, which has the potential to revolutionize the way we treat T1D.
Two-part cell therapy strategy
In T1D, beta cells are destroyed because the immune system no longer recognizes them as part of the body. For critically ill patients who are difficult to control with exogenous insulin, doctors can perform islet cell transplants containing beta cells.
However, this option presents two major challenges. First, islet transplantation is dependent on donor tissue, and there are not enough beta cells available. To address this shortage, the research team is producing their own stem cell-derived islet cells in the lab.
The second problem is immune rejection. Transplanted beta cells, like any other foreign tissue, can be attacked by the immune system. This is where Ferreira’s immunoengineering expertise becomes essential. Tregs naturally help calm the immune response. Ferreira modifies these cells with a CAR that recognizes a specific surface protein located on the beta cells. This acts like a GPS signal, directing Tregs precisely to the transplanted cells.
Once there, engineered Tregs act as targeted “bodyguards” to protect beta cells from immune attack. This interaction works like a lock and key. When a receptor on a Treg matches a protein on a beta cell, it signals the immune system to stop. Beta cells and Tregs together form a protective partnership that helps maintain insulin production after transplantation.
Avoidance of immunosuppressants
One of the major advantages of this combined cell therapy is that it eliminates the need for immunosuppressants. These drugs are usually needed after transplantation, but they carry significant long-term risks, especially for children.
Lab-generated beta cells also have the potential to solve the long-standing shortage of donor tissue. Currently, a single transplant requires beta cells from three or four donors, but most organ transplants require a one-to-one match. In contrast, the beta cells developed by the research team can be produced, frozen and stored in the lab without compromising quality. This opens the door to scalable and reliable supply for future treatments.
The ultimate goal is to create a complete commercially available treatment that combines genetically engineered Tregs with lab-grown beta cells. Such treatments have the potential to be widely disseminated and administered through transplantation.
“We’re trying to develop a treatment that works for all people with type 1 diabetes at all stages, even those who have had the disease for many years and have no beta cells left,” Ferreira said.
Test durability and long-term effects
Clinical application of this treatment will require time and further research. Several questions remain, including how long the protective effect lasts. In preclinical studies using humanized mice, effects lasted up to a month, the longest duration studied to date. The new funding will allow researchers to look at ways to extend this protection, improve dosing methods, and determine whether multiple doses can produce longer-lasting effects.
By combining stem cell biology, gene editing, and immune regulation, the team is developing multiple treatments. They are building a framework to teach the body to repair itself. If successful, this research could ultimately free patients from daily insulin injections and move type 1 diabetes treatment from lifelong management to true cure.
The effects extend beyond diabetes. Success could mean major advances in regenerative medicine and immune-based treatments.
“I think this has the potential to change the way medicine is done,” Ferreira said. “Instead of treating the symptoms, we can actually replace the missing cells. By doing this research, we may be able to better understand how T1D begins, how it develops, and how it can be treated.”
