Diabetes is a chronic disease characterized by an increase in glucose in the blood. To compensate, type I diabetes mellitus (T1DM) patients need to take insulin several times a day. Among Type II diabetes mellitus (T2DM) patients, one in six patients eventually needs to take insulin. For these patients (about 80 million worldwide) the disease is ever-present in their daily lives, requiring multiple glycaemia measurements, calculations of carbohydrate intake, and insulin injections. Moreover, despite intensive insulin therapy, microangiopathic complications remain a reality for diabetic patients and a small proportion of patients develop brittle diabetes, a rare form of type I diabetes exposing patients to high glucose variability and severe metabolic events such as hypoglycemic coma or keto-acidosis. The key therapeutic issue in diabetes mellitus type I and II is glycaemic control. Reductions of constant self-control, of insulin self-injections, and of long-term complications would have tremendous benefit for the patient’s quality of life. In this context, islet transplantation represents a hope for millions type I and some of type II diabetic patients offering the perspective of an endogenous regulation of glycemia without insulin injection. Islet transplantation or cell therapy of type I diabetes is a technique now validated for the management of unstable diabetic patients and it exposes patients to a lower morbidity and mortality than the pancreas transplantation. The weakness of this therapy remains the organ source and the requirement for life-long immunosuppression, which is often associated with serious adverse events such as hypertension, increased susceptibility to infections and increased risk of cancer. The extension of cell therapy of type I diabetes to the greatest number of patients with type I diabetes is conditioned by the discontinuation of immunosuppressive therapy. Many projects focus on islet encapsulation, which provides an innovative perspective to avoid immunosuppression during transplantation. The concept of encapsulation involves applying a physical barrier between cells and the immune system. Three types of encapsulation are distinguished: macroencapsulation, which consists in grafting the islands in a macro-chamber, microencapsulation, which consists in isolating each islet within a single capsule and Nanoencapsulation which consist of coating each islet with a nanolayer of biomaterial. These projects represent a real challenge since, for over 30 years, several encapsulated islet approaches have been envisaged without, unfortunately, leading to the development of clinically effective products. Obstacles to overcome are represented to capsules fibrosis and islet necrosis within the capsule. These difficulties are addressed in the BIOCAPAN project.
In BIOCAPAN we aim at developing an innovative treatment, based on the implantation of smartly microencapsulated allogeneic pancreatic islets (cluster of cells secreting insulin) =, which will allow an effective long-lasting blood glucose normalization and stabilization, without the need for immunosuppressive therapy. We have three objectives:
1. Design a complex GMP-grade bioactive microcapsule that will enhance biocompatibility, functionality and survival of transplanted allogeneic islets, in order to reach 2-years of insulin injection free treatment, without the need for immunosuppressive therapy.
2. Establish a method to encapsulate freshly harvested islets quickly, using a GMP-grade platform, to provide standardized and reproducible bioactive microcapsules.
3. Establish an Investigational Medicinal Product Dossier (IMPD) in accordance with the provisions of the Advanced Therapy Medicinal Products (ATMP) Regulation
