First T1D Functional Cure Using Immunosuppressive Therapy

Trial participant Marlaina Goedel lived with T1D for over 25 years. In an interview with CBS News, Goedel said she applied for the islet surgery after years of battling high and low blood sugar levels.

On July 17, 2024, doctors injected the islet cells into Goedel’s liver. Three weeks later, she was off external insulin, and several months later, she remains insulin-independent following an immunosuppression regimen.

Immunosuppression Regimen   

In the clinical islet transplant study, participants received islet transplants combined with induction therapy, mycophenolate mofetil (MMF) and tegoprubart, given every third week through intravenous (IV) infusions.

The first two of three patients treated with tegoprubart as part of the immunosuppression regimen achieved insulin independence and normal hemoglobin A1c levels post-transplant. The third participant has decreased insulin usage by 60% and is en route to insulin independence. 

Islet Engraftment

An islet engraftment is where the transplanted islet cells take root in the liver to begin insulin production. The islet engraftment in the first two subjects with tegoprubart was estimated to be three to five times higher than three comparable subjects who received tacrolimus-based immunosuppression, suggesting the treatment with tegoprubart was less toxic.

The recent treatment was well received in participants with no unexpected adverse events, severe hypoglycemic episodes, or graft rejection.

The University of Chicago Medicine’s team recently presented its success at the International Pancreas and Islet Transplantation Association (IPITA), Harvard Stem Cell Institute (HSCI), and Breakthrough T1D’s (formerly JDRF) 5^th Annual Summit on Stem Cell Derived Islets.

Piotr Witkowski, M.D., Ph.D., Director of the Pancreas and Islet Transplant Program at UChicago Medicine and one of the study’s lead investigators said, “For more than 30 years, we have been looking for options that can deliver target levels of immunosuppression without the side effects associated with the standard of care, including toxicity to the kidneys, central nervous system and islet cells, and increased risk of diabetes and hypertension.”

Witkowski is hopeful they can expand the pool of patients for this life-changing transplant surgery. “These data further support tegoprubart as a novel immunosuppression option that can play a central role in advancing islet transplantation as a potentially transformational alternative for subjects with type 1 diabetes.”

Additionally, Breakthrough T1D Chief Scientific Officer Sanjoy Dutta, Ph.D., said, “Islet replacement therapies are a key priority for Breakthrough T1D, and we’re committed to driving research that moves us toward a world where these therapies are available to the broader T1D community. Breakthrough T1D is proud to fund and support this research. It is encouraged by the tegoprubart study showing that subjects who received islet transplants with a tacrolimus-free immunosuppressive regimen are making insulin again.”

Islet Cell Transplantation for T1Ds

Pancreatic islet cell transplantation is a minimally invasive procedure in which healthy pancreatic islets (insulin-producing beta cells) are injected to control tight blood glucose.

In some cases, pancreatic islets containing insulin-producing beta cells are isolated from the pancreas of a deceased organ donor and infused through a small catheter into the patient’s liver. The islet cells port in small blood vessels in the liver and release insulin. Post-procedure, subjects need immunosuppression therapy to prevent transplant rejection.

Immunosuppressive Therapy

Immunosuppressive therapy is a drug regimen for individuals that lowers the body’s immune response. The medication is designed to stop the immune system from attacking the transplanted organs, cells, and tissues.

The side effects of immunosuppressive treatment is that the immunosuppressants weaken the body’s immune system, making individuals more susceptible to infections. They can also increase the risk of certain cancers and other complications like high blood pressure, cholesterol and gastrointestinal issues.

About Eledon Pharmaceuticals 

The biotechnology company Eledon Pharmaceuticals is a clinical-stage firm with immunology expertise. Eledon develops therapies to protect and prevent rejection of transplanted organs, as well as treat disorders like amyotrophic lateral sclerosis (ALS).

Eledon’s most promising lead compound in development is tegoprubart, an anti-CD40L antibody. The drug tegoprubart has aided how the immune cells that cause transplant rejection communicate. It’s recently been used for the first-ever pig kidney xenotransplant and the second-ever pig heart xenotransplant.

The study's funding includes grants from Breakthrough T1D (formerly known as JDRF) and The Cure Alliance. Eledon has also received $85 million in financing from several new and existing investors, including BVF Partners, LP, RA Capital Management, Frazier Life Sciences, Blue Owl Healthcare Opportunities, First Light Asset Management and T1D Fund: A Breakthrough T1D Venture.

Study Overview

Results from the study highlight the three T1D pancreatic islet transplant recipients treated with tegoprubart have achieved a functional cure. Two have achieved insulin independence without the aid of the standard immunosuppressant tacrolimus. Compared to other tacrolimus-based immunosuppression regimens, the safety and efficacy profile appears promising.

The first T1D, a 42-year-old female, reduced her A1c from 8.4% to 6.0% within 90 days, and insulin use decreased from 80 to 16 units daily. After a second transplant at 16 weeks, she achieved insulin independence, with an A1c of 5.4%. The second study participant, a 30-year-old T1D female, discontinued insulin four weeks post-transplant, with her A1c improving from 8.5% to 5.8% at seven weeks.

Additionally, the third participant, a 37-year-old male, was discharged on the third day after his transplant procedure with a reduced insulin regimen of 29 units, down from 90.

All Roads Lead to Rome

The idiom ‘all roads lead to Rome’ can be applied to the path for a T1D cure. There are many ways to achieve the same result. With every technological directive, research activity, and novel innovation, we are one step closer to curing type 1 diabetes for all.