Juvenile (Type-1) Diabetes (T1D)
Diabetes has become an epidemic. Currently 62 million adult diabetes patients live in North America, 66 million in the European Community (EC), 73 million in India and 110 million in China. The prevalence of diabetes is increasing, and Asian countries are thought to demonstrate the highest increase.
The T1D community in Northern America includes 5 million Americans. Eight million T1D are leaving in Europe, 4 millions in India and the numbers are on the rise by an annual factor of 3.4%.
Diabetes is a major cause of severe clinical complications. It is direct cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. Overall, about 4 million deaths are reported annually as direct cause of the disease.
Besides human burden described by premature mortality and lower quality of life, diabetes also imposes a significant economic impact on healthcare systems. International economic burden is huge and the total world annual disease-related expenditure exceeds 700B$. In China, most of new T1D cases are diagnosed in adults which is forecasted to further increase the economic burden.
T1D is characterized by the inability of the pancreatic islets to produce insulin. Therefore, insulin is the only treatment for this type of the disease. The hormone is administered into the subcutis using hypodermic injection or pump driven perfusion following self-monitoring of blood glucose using finger-stick blood samples, test strips or portable meters. The procedure is both annoying and time consuming. Moreover, insulin overdose is a direct cause of life-threatening low blood glucose (hypoglycemia).
Insulin therapy is considered as a treatment for T1D, not as a cure of the disease. Organ transplantation, in the form of whole organ or islets only is currently the only available methods to cure diabetes.
Clinical islets transplantation from deceased donors was established in the early 90’s as an experimental protocol by Prof Paul Lacy (Missouri). However, success rate was low. A decade later, a group from Edmonton, led by Prof James Shapiro, established a steroid-free immunosuppression therapy. Using this protocol, they greatly improved long-term viability and performance of transplanted islets. Transplanted patients are reported as normoglycemic and insulin-free for a few-year period.
Two major drawbacks are associated with the Edmonton protocol. Firstly, it is dependent on large number of donor islets – average of 2 donors per patient. In a world of large shortage of donor organs this fact severely limits number of transplantations. Secondly, in order to prevent rejection by the host immune system, life-long use of immunosuppressive drugs is a mandatory request. Notably, long-term use of these drugs is associated with significant morbidity (e.g. malignancies, hypertension, and opportunistic infection). As a result, human allogeneic islet transplantation has not been widely adopted by the medical community. Limited number of clinical procedures have been performed globally during a period of almost two decades.