City of Hope offers islet cell transplant program to cure type 1 diabetes

For patients with severe type 1 diabetes, a strict diet and insulin shots are sometimes not enough to sufficiently control their disease. What they need are insulin-producing cells of their own - currently only available through a still-experimental procedure known as islet cell transplantation. Physicians in the newly launched Diabetes & Metabolism Research Institute at City of Hope are now providing this transplantation to suitable candidates through a clinical trial that they believe will be the first step in a multipronged effort to permanently cure type 1 diabetes.

"We are one of only a few islet cell transplant programs in the country," said Fouad Kandeel, M.D., Ph.D., chair of the Department of Clinical Diabetes, Endocrinology & Metabolism at City of Hope, who is leading the islet cell transplantation trial. "This trial, in addition to providing a much needed potential cure for patients with severe type 1 diabetes, will also be vital in opening the door to other major studies to address the medical needs of these patients."

The new phase I/II trial is open to adults with type 1 diabetes who have had the disease for more than five years and who experience frequent episodes of hypoglycemia or hypoglycemia unawareness, in which blood sugar drops precipitously without corresponding symptoms. Diabetic patients who have hypoglycemic unawareness are at risk of injuries and accidents, because the drop in their blood sugar can go undetected until they suddenly lose consciousness.
The goal of the trial is to further evaluate the effectiveness of transplantation as a treatment and possible cure for type 1 diabetes. Researchers also hope to gain a better understanding of the mechanisms of islet cell rejection if it occurs.

"The immune-suppression strategy that is being used in the current trial is considered a significant improvement over the protocol used in previous islet cell transplant trials," Kandeel said. The strategy, which research suggests will result in better islet cell function in transplanted patients, is intended to do more than deplete "disease-causing immune cells," that is, the immune cells that attack the pancreas and kill insulin-producing cells. It also is intended to spare regulatory T cells, a class of immune cells that can prevent the body's attack on insulin-producing cells.

In previous studies of this strategy, 60 percent of patients were able to produce sufficient insulin on their own five years after transplant. Researchers believe that even those patients who still require supplemental insulin through injections will nonetheless likely have improved blood glucose control from partial islet function, he said.

Past islet cell transplants using different immune suppression approaches resulted in only 20 percent of patients producing sufficient insulin on their own.

Ultimately, City of Hope researchers hope to conduct other in-human clinical trials designed to benefit recipients of islet cell transplant. One study would aim to expand the growth of islet cells in the body through a medication developed at City of Hope that stimulates the growth and generation of new insulin-producing cells within the transplanted islets.

The second study would test an approach to expand and educate patients' own regulatory T cells to protect the transplanted islets and prevent reactivation of the disease-causing cells. These improved cells would then be infused back into type 1 diabetes patients.