New therapy after islet cell transplant shows promise for people with Type 1 diabetes

For Dr. Daniel Gilada, a husband, physician and soon-to-be father of four, living with Type 1 diabetes had become “overwhelming.”

“I felt so bad that it was becoming my new norm,” said Gilada, diagnosed with Type 1 diabetes nearly 20 years ago as a high school senior. “Diabetes is in every single decision you make, from the time you wake up until the time you go to sleep.”

In addition to taking insulin to control their blood glucose levels, people with Type 1 diabetes must measure their levels multiple times a day, by either finger pricks or wearing a continuous glucose monitor. Common complications of Type 1 diabetes include hypoglycemia, or low blood sugar, and diabetic ketoacidosis.

Marlaina Goedel, who was diagnosed with Type 1 diabetes at age 5, said for her, the disease was not only controlling but also endangering her life.

"I've crashed my car into a brick building before having a diabetic attack while driving," said Goedel, now 30. "My significant other, who I've been with for 16 years, has had to pick me up out of bed from [my blood sugar] crashing in my sleep more times than I can count. My daughter has had to help lift me up off the kitchen floor and give me something to drink from my blood sugar crashing."

Goedel said her diabetes became so uncontrollable that each night, she fell asleep wondering if she would wake up alive the next morning.

Now, thanks to a potential medical breakthrough, after decades of fighting type 1 diabetes, Goedel is no longer using insulin and Gilada has decreased his insulin use dramatically.

"[My doctor] said, ‘Mark it on your calendar. Today is the day. Stop all insulin,'" Goedel said of the lifechanging moment. "I just went quiet and finally said, ‘I’m here. I’m in shock. I’m going to need you to repeat that.’"

Goedel, like Gilada, underwent an islet cell transplant through a clinical trial at the University of Chicago Medicine Transplant Institute, in collaboration with the University of Miami Diabetes Research Institute and is funded by The Cure Alliance and Breakthrough T1D (formerly Juvenile Diabetes Research Foundation).

New data from the clinical trial that is testing an investigational therapy after islet cell transplant was presented in Boston on Tuesday, and showed early signs of success in the first three patients, which include Goedel and Gilada.

The first two recipients have achieved insulin independence and have normal hemoglobin A1C levels, a measure of average blood glucose, after transplant, according to the data, presented at the 5th Summit on Stem Cell Derived Islets.

The third recipient decreased insulin use by more than 60% three days following the procedure.

Islet cell transplants aren’t new, it’s been possible for decades, but the antirejection medication currently used can be toxic to the transplanted cells, potentially making it less effective over time.

The transplant works by taking islet cells that produce insulin from a deceased organ donor’s pancreas and infusing them into small blood vessels in the recipient’s liver through a catheter in a minimally invasive procedure. The infused cells lodge into those small blood vessels and start producing insulin.

Type 1 diabetes is thought to be caused by an autoimmune response that destroys the insulin-making cells in the pancreas, according to the U.S. Centers for Disease Control and Prevention. As a result, people with type 1 diabetes are dependent on external sources of insulin, delivered via shots or an insulin pump, to stay alive.

After islet cell transplants, because cells from one person are transplanted into another, medication that suppresses the immune system is needed to prevent the recipient’s body from rejecting it.

The clinical trial in which Goedel and Gilada are taking part is testing a new monoclonal antibody, called tegoprubart. Its goal is to replace the old antirejection drug.

Tegoprubart, manufactured by Eledon Pharmaceuticals, Inc., is an investigational anti-CD40L monoclonal antibody, meaning it is made in a lab, and works by tricking the immune system to recognize the transplant as “self” to avoid immune rejection.

The researchers say these are potentially the first human cases of insulin independence achieved using an anti-CD40L monoclonal antibody therapy without the use of tacrolimus, the current standard of care for prevention of transplant rejection.

“These data are another step in our quest to achieve a path for functional cures in type 1 diabetes,” said Piotr Witkowski, M.D., Ph.D., director of the Pancreas and Islet Transplant Program at University of Chicago Medicine, and one of the study’s lead investigators, said in a statement Tuesday.

The function of the transplant was also three to five times higher than three comparable subjects who received tacrolimus-based immunosuppression, which researchers say suggests the new therapy may be less toxic to the transplanted islets as hoped, resulting in improved graft survival and function.

While this early success holds hope, the researchers say they face regulatory barriers in the United States that prevent more people from receiving islet cell transplants because they are regulated through the U.S. Food and Drug Administration as a biologic drug, not an organ transplant.

These barriers could prevent people from accessing islet cell transplants using this investigational therapy outside of a clinical trial one day, even if this clinical trial is successful.

Even with potential barriers ahead, the early results of the clinical trial do offer hope for a future cure for Type 1 diabetes that is already helping people like Gilada and Goedel live better lives.

Type 1 diabetes impacts more than 2 million adults and kids, according to the CDC.

While Type 1 diabetes is often diagnosed in children, teens and young adults, it can develop at any age. Long-term complications from the disease can include increased risk of nerve damage, kidney disease, cardiovascular disease and stroke.

“I haven't felt this normal in 19 years,” Gilada said of his life post-transplant, adding that he had not sought out an islet cell transplant previously because he didn’t want to take the required immunosuppressive medication due to the side effects.

“You have this daily renewal, this daily energy, motivation, whatever you want to call it, from help from someone else,” Gilada said, crediting his donor. “Thank you. I don't know what else to say, thank you. I want to tell their family. Thank you.”

Goedel said that since the transplant, she feels like she is fully able to "breathe" for the first time since being diagnosed with Type 1 diabetes 25 years ago.

"We’re all very happy, honestly to not have to worry anymore. We can breathe," she said of herself and her loved ones. "I hated everybody always worrying about me and wanting to know where I was at and what I was doing. It’s been so freeing and liberating, honestly."

She added, "Nobody should live with that disease, and I know that even more now."

Jade A. Cobern, MD, MPH is a physician board-certified in pediatrics and preventive medicine and a medical fellow of the ABC News Medical Unit.