Type I Diabetes

Type I diabetes is an autoimmune disease wherein the immune system erroneously targets and destroys the insulin secreting beta cells of the pancreas and as a consequence requires patients with this disease to treat themselves with daily injections of insulin to control their blood sugar levels. To treat this disease, gene therapy investigators are currently studying approaches to efficiently transfer the insulin gene into other cells such as the liver, stomach, or intestines. Alternatively, cell therapy approaches for this disease are focused on developing the most efficient methods for the isolation of pancreas beta cells or appropriate stem cells, appropriate location for cell transplant, and improvement of their survival upon infusion. Alternatively, gene and cell therapy scientists are developing methods to reprogram some of the other cells of the pancreas to secrete insulin. Currently ongoing clinical trials using these gene and cell therapy strategies hold promise for improved treatments of type I diabetes in the future.

Type 1 diabetes is an autoimmune disease in which the immune system aberrantly recognizes and destroys most of the insulin secreting beta cells of the pancreas. This disease is different from other forms of diabetes because of this underlying autoimmunity. Beta cells produce insulin which is critical for maintaining normal sugar levels and sugar distribution in the body. Gene therapy scientists are investigating the optimal and safest method for transferring an efficiently expressing insulin gene into other cells, including those in the liver, stomach, or intestines. Induced pluripotent stem cells (iPSCs) have been isolated from type 1 diabetic subjects; they are a useful tool to study disease mechanism. Furthermore, different laboratories are trying to develop efficient protocols to induce the differentiation of iPSCs into beta-like cells. These studies are currently being conducted in vitro and in animals and not yet in clinical trials. The main challenges for this approach include (1) achieving the proper regulation of expression by the insulin gene to make the proper amount of insulin, and (2) avoiding a repeated aberrant immune response to these gene modified cells, an autoimmunity that previously resulted in the killing of the patient’s insulin-producing beta cells. Alternatively, other preclinical studies are investigating gene based therapies to overcome the patient’s aberrant immune response to pancreatic beta cells through the delivery of genes encoding immune suppressive proteins, called cytokines, such as TGF beta and interleukin 10 into the pancreas which in turn may suppress this autoimmune response allowing the patient’s own insulin secreting beta cells to survive.

Furthermore, the pancreas also contains other cells called exocrine cells which secrete digestive enzymes. Significantly, these cells remain intact in patients with type 1 diabetes and thus, could potentially be gene modified to secrete insulin as an alternative genetic approach to treating this disease. Recently, gene therapy researchers have identified 3 genes that can convert adult pancreatic exocrine cells into pancreatic beta cells. In pre-clinical animal models, these reprogrammed exocrine cells were identical to beta cells in size, shape and expression of essential genes, and resulted in reduced blood sugar levels and improved sugar distribution. Other cells that have been shown to be susceptible to reprogramming to become beta-like cells include pancreatic alpha cells, pancreatic ductal cells and adult stem cells in the liver.

In addition to gene transfer strategies, a variety of cell therapy approaches are also being investigated for the treatment of type 1 diabetes. Multiple clinical trials are currently recruiting patients to assess the ability of transplantation of various cell populations to normalize blood sugar levels, reduce disease symptoms, and assess safety. Some trials utilize patient derived cells (termed autologous cells) for therapy, while others utilize donor derived cells (termed allogeneic cells) obtained from other humans. Currently, there are over 20 ongoing human clinical trials utilizing one of the following cell sources to transfer or generate pancreatic beta cells in patients with type I diabetes: allogeneic pancreatic beta cells, mesenchymal stem cells, cord blood stem cells, or autologous adipose-derived stem cells. Several cell therapy trials also include different regimens of immunosuppressive medications designed to abrogate the aberrant anti-beta cell autoimmune response, and / or specific nutrients (vitamin D, omega 3 fatty acids which are usually low in diabetics) designed to improve clinical outcomes and reduce side effects. In addition, several clinical studies testing the ability of specific cell populations to reduce the immune response against the beta cells are currently ongoing. Furthermore, ongoing studies using either autologous or allogeneic hematopoietic stem cell transplant, with an aim to delete beta cell targeted autoimmune cells, may additionally provide promising data to expanding this approach further either alone or in combination with other gene and cell based approaches to treat patients with type I diabetes. Collectively, these multiple gene and cell based approaches represent the advent of a new and promising era in diabetes research. As promising preclinical studies mature into clinical studies, and as the multiple ongoing clinical studies accrue data, there are clear signs that these novel gene and cell based innovative approaches hold true promise for advanced and improved treatment approaches for patients with type I diabetes.

As the Juvenile Diabetes Research Foundation, one of the first advocate groups for diabetes research emerging from a small group of lay volunteers, is reaching 40 years of existence, these novel gene and cell based areas of investigation raise a realistic hope for the cure of this devastating disease in the foreseeable future.

For more information on diabetes, please visit the following websites:

American Diabetes Association
Juvenile Diabetes Research Foundation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
World Diabetes Foundation

Please consult your physician before making any medical decisions.