An experimental immunosuppressive drug, tegoprubart, is showing promise in improving the success of islet cell transplants for patients with Type 1 diabetes. The study, presented at the Summit on Stem Cell Derived Islets in Boston, highlights the potential of tegoprubart to enhance islet cell engraftment and reduce the need for insulin injections in transplant recipients.
Tegoprubart in Islet Cell Transplantation
Type 1 diabetes patients often require islet cell transplants from deceased donors to restore insulin production. However, rejection of these transplanted cells by the recipient's immune system remains a significant challenge. Researchers, led by Dr. Piotr Witkowsky at the University of Chicago Medicine, explored the use of tegoprubart, an immunosuppressive drug, to mitigate this rejection.
Tegoprubart, the same drug used in the first transplant of a pig kidney into a human patient earlier in 2024, was administered to three patients undergoing islet cell transplants. Encouragingly, two patients achieved insulin independence with normal A1C levels at 18 weeks (following a second transplant) and 4 weeks, respectively. The third patient experienced a 60% reduction in insulin needs shortly after the transplant and continues to be monitored.
Improved Outcomes Compared to Standard Immunosuppression
Dr. Witkowsky noted the limitations of previous immunosuppressants, stating, "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." The small study also reported no side effects, and the transplanted islet cells were three to five times more likely to engraft and produce insulin than cells transplanted in people who had received the current immunosuppressive drug tacrolimus.
"We don’t need to adjust doses to control toxicity like we do with tacrolimus," says Witkowsky. "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."
Mechanism and Further Research
Tegoprubart is administered as a 15-minute infusion every three weeks and functions by suppressing the immune response to foreign proteins in the transplanted organ. Eledon, the company developing tegoprubart, is conducting clinical trials to evaluate its safety and efficacy in kidney transplants, animal organ transplants, and ALS.
Previous versions of the drug had increased the risk of blood clots, but continued research has reduced that risk and improved tegoprubart's immune-suppressing ability. Witkowsky aims to secure funding for further studies, planning to expand the cohort by six patients to better understand the long-term survival of islet cells and the drug's ability to restore insulin-making functions. "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."
