A better drug could make transplants more successful

OOrgan and cell transplants are potentially life-saving treatments for a variety of medical conditions. However, their success depends on how long the transplanted cells or tissue can survive in their new host. Drugs that suppress the immune system to minimize rejection must strike a delicate balance: They must be strong enough to stop the recipient's immune system from destroying the donated material and not too strong to cause toxic reactions .

In a study presented at the Summit on Stem Cell Derived Islets in Boston, researchers report encouraging results with an experimental immunosuppressant in people with type 1 diabetes. People with this disease no longer produce enough insulin in their pancreas to break down the sugar in the foods they eat and must monitor their blood sugar levels and inject themselves with insulin for the rest of their lives. In some cases, the insulin shots lose their effectiveness and patients need more aggressive treatment: usually a transplant of islet cells – which produce insulin in the pancreas – from a deceased donor. But many patients ultimately reject the transplanted cells when their body's immune system sees them as foreign and begins attacking them.

In the latest study, researchers led by Dr. Piotr Witkowsky, professor of surgery and director of pancreas and pancreatic islet transplantation at the University of Chicago Medicine, performs islet cell transplants with a different drug to suppress the recipients' immune systems. The drug, Tegoprubart, was the same one used in the first transplant of a pig kidney into a human patient in early 2024. In the current study, three patients received islet cell transplants with Tegoprubart; two no longer required insulin injections and achieved normal A1C levels at 18 weeks (and after a second islet cell transplant) and four weeks, respectively, while the third patient reduced his insulin requirements by 60% several days after transplantation and is still being monitored.

“We have been performing islet cell transplants from deceased donors for 24 years,” says Witkowski. “Initially there was great hope that patients might come off insulin, but we realized that the immunosuppressants we were using were not optimal and over time patients were losing their immunosuppression [transplanted] Islet cells.”

Read more: The paradox of how we treat diabetes

The small number of patients in the Tegoprubart study reported no side effects, and the transplanted islet cells were three to five times more likely to proliferate and produce insulin than cells transplanted into people receiving the current immunosuppressant drug tacrolimus had. “We don’t need to adjust dosage 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 hope is high.”

Witkowsky was inspired to try Tegoprubart in islet cell transplants after its success in kidney transplant patients — including the first porcine kidney surgery and more traditional kidney transplants using donated human organs. Studies showed that 60 kidney transplant patients who received Tegoprubart experienced no rejection or toxicity. “The kidney function of these transplant patients appeared to be better with Tegoprubart than with tacrolimus, and we believe we can achieve similar results in type 1 diabetes,” he says.

The new drug is an antibody that is administered as a 15-minute infusion every three weeks. It works by suppressing the immune response to foreign proteins in a transplant from a donor. It is not yet approved; The developer company Eledon continues to study it in clinical trials to evaluate its safety and effectiveness in kidney transplants, animal organ transplants and ALS.

Previous versions of the drug studied more than two decades ago increased the risk of blood clots, but continued research has reduced that risk and improved Tegoprubart's immunosuppressive effects. Witkowsky hopes to find funding to continue studying these initial patients and add about six more to better understand how long the islet cells can survive and whether the drug can buy the transplanted cells enough time to engraft the patients' insulin production functions and restore as close to normal as possible. “Unfortunately there are none [real] Therapy for type 1 diabetes patients,” he says. “The key thing is that we know that the cells have the potential to work – they actually work. The problem remains immunosuppression. And now we have a drug that can help us a lot.”