An experimental immunosuppressive drug, tegoprubart, is showing promising results in improving the outcomes of islet cell transplants for individuals with Type 1 diabetes. The study, presented at the Summit on Stem Cell Derived Islets in Boston, indicates that tegoprubart may offer a more effective way to prevent rejection of transplanted cells, potentially reducing or eliminating the need for insulin injections for these patients.
Improved Outcomes with Tegoprubart
Researchers, led by Dr. Piotr Witkowsky at the University of Chicago Medicine, conducted islet cell transplants using tegoprubart to suppress the recipients’ immune systems. In the study, two patients no longer required insulin injections after 18 weeks and four weeks, respectively, achieving normal A1C levels. The third patient experienced a 60% reduction in insulin needs shortly after the transplant and continues to be monitored.
"We have been doing deceased donor islet cell transplants for the last 24 years," said Witkowski. "There was a lot of hope at the beginning that patients might come off insulin, but we realized that the immune suppressants we were using were not optimal, and over time, patients were losing the [transplanted] islet cells."
Tegoprubart's Mechanism and Benefits
Tegoprubart, administered as a 15-minute infusion every three weeks, functions by suppressing the immune response to foreign proteins in a donor transplant. The study reported no side effects among the small number of patients, and the transplanted islet cells were three to five times more likely to engraft and produce insulin compared to cells transplanted in patients receiving tacrolimus, a current immunosuppressive drug.
"We don’t need to adjust doses to control toxicity like we do with tacrolimus," Witkowsky noted. "And their islet function is at least three times better compared to patients receiving tacrolimus because there is no toxicity. These results are preliminary, but the hope is great."
Inspiration from Kidney Transplant Success
Witkowsky's decision to explore tegoprubart in islet cell transplants was influenced by its success in kidney transplant patients, including the first pig kidney transplant. Studies involving 60 kidney transplant patients receiving tegoprubart showed no rejection episodes or toxicity. "The kidney function in those transplant patients seemed to be better with tegoprubart compared with tacrolimus, and we think we can get similar results with Type 1 diabetes," he explained.
Ongoing Research and Future Directions
Eledon, the company developing tegoprubart, is continuing clinical trials to evaluate its safety and efficacy in kidney transplants, animal organ transplants, and ALS. Earlier versions of the drug had increased the risk of blood clots, but further research has mitigated this risk and enhanced its immune-suppressing capabilities. Witkowsky aims to secure funding to continue studying the initial patients and expand the study to better understand the long-term survival of islet cells and the drug's ability to restore insulin-making functions.
"Unfortunately there is no [real] therapy for type 1 diabetes patients," he stated. "The bottom line is that we know the cells have the potential to work—they do work. The problem remains immunosuppression. And now we have a medication that may help us a lot."
