City of Hope researchers developed a combination therapy to treat late-stage type 1 diabetes that appears to offer a potential lifetime cure for the disease without toxic side effects. The laboratory study was published as a cover story in the May 9 edition of Science Translational Medicine.

Jeremy Racine, left, Defu Zeng, Ivan Todorov and Miao Wang aim to harness immune cells. (Photo by Matthew Stringer)

“Our findings indicate that it is possible to cure late-stage type 1 diabetes by stopping autoimmunity and regenerating insulin-secreting beta cells,” said Defu Zeng, M.D., associate professor in the Division of Diabetes, Endocrinology & Metabolism and Department of Hematology & Hematopoietic Cell Transplantation.

VIDEO: Researchers develop potential cure for advanced type 1 diabetes

About 20 million people worldwide have type 1 diabetes. In type 1 diabetes, the body’s immune cells mistakenly attack and kill beta cells, part of the clusters of cells in the pancreas called islets. These cells produce insulin needed to turn food into energy. No treatment except islet transplantation has been effective for late-stage diabetes, but these transplants are neither easily available nor permanent.

Other developing therapies for type 1 diabetes either target the autoimmune condition or look to replace the destroyed beta cells, but not both together. These approaches have showed only limited success.

“While transplanting islet cells from another person can provide insulin independence, the effect lasts only about three years due to chronic rejection of the graft cells,” said Zeng, the study’s principal investigator. “Additionally, there is a shortage of islet donors.”

The researchers’ strategy strives to both block the immune system from destroying beta cells and to stimulate the growth of new beta cells. The combination therapy begins with timed doses of special proteins that target certain immune cells, called T cells, which attack beta cells. Then scientists infuse bone marrow from a donor to induce what is called “mixed chimerism.”

Mixed chimerism is a condition in which a patient’s immune system is made up of both the patient’s own cells as well as new cells from the donor bone marrow.

Healthy immune cells replace the patient’s defective immune cells, stopping the autoimmune condition. Unlike traditional bone marrow transplants, this approach requires no radiation or high-dose chemotherapy.

Because patients with chronic type 1 diabetes often have too few working beta cells left to regenerate healthy cells, the researchers follow up the mixed chimerism with growth hormones. These can spur new beta cells to develop from stem cells, as well as stimulate the remaining beta cells to multiply, reestablishing normal insulin production and management.

Zeng and his team were able to reverse late-stage type 1 diabetes in lab mice through this strategy, not only halting the autoimmune process, but also helping new beta cells grow. As a result, diabetes was reversed in 60 percent of the diabetic mice that received the experimental therapy, while none of the control mice recovered from their disease, said Miao Wang, M.D., Ph.D., first author of the study and a postdoctoral research fellow in Zeng’s lab.

The mice that received the therapy had 10 times higher beta cell mass, three times higher insulin levels and improved insulin sensitivity and beta cell survival compared to the untreated mice.

Zeng is pursuing additional lab studies of the therapy, with the goal of gaining approval for human clinical trials.

The collaborative study also included researchers from the University of Florida Diabetes Center of Excellence in Gainesville, Fla., University of Florida College of Medicine in Gainesville, Fujian Institute of Hematology at Fujian Medical University Union Hospital in Fuzhou, China, and Nanfang Hospital at Southern Medical University in Guangzhou, China.

The study was supported by funding from the Iacocca Family Foundation and private donations from Todd and Karen Wanek as well as the Davis family.