Periodic Reporting for period 1 - TheLiRep (Exploring the Potential for Therapeutic Lineage Reprogramming of Diabetes)
Periodo di rendicontazione: 2015-05-01 al 2016-10-31
In the “TheLiRep” ERC Proof-of-Concept (PoC) project, we performed the initial proof-of-concept experiments required for translating from mouse to human a novel strategy to generate pancreatic cells based on lineage reprogramming of adult liver cells using one single transcriptional regulator. Overall, the ERC PoC funding enabled to further exploit my ERC idea, to build a solid intellectual property foundation and to develop a strategic plan to move this experimental data closer to the clinic. The “TheLiRep” project will have indeed direct implications in developing an autologous cell-based therapy of diabetes based on converting adult liver cells of diabetic patients into functional pancreatic β cells.
Diabetes mellitus represents a worldwide extremely important public health problem considering its high prevalence, the serious complications triggered by the disease, the associated rate of mortality and, not the least, the high economic and social costs. Despite the growing burden of diabetes, no cure has yet been found for the disease and the conventional treatments, based on exogenous insulin or oral agents, may control and delay but not prevent the disease complications. Thus, mortality and morbidity have steadily been increasing. Two major groups of diabetes have been defined: type 1 and type 2. Type 1 diabetes is an autoimmune disease that results in the destruction of the insulin-producing pancreatic β cells. It usually presents in childhood and patients require lifelong insulin. Type 2 diabetes, the most common form of the disease, is characterized by a combination of resistance to insulin action and inadequate compensatory insulin secretory response, leading to a decline in insulin production and later pancreatic β cell failure. The ability of cadaveric islet transplantation to restore euglycemia in patients with severe type 1 diabetes, known as the “Edmonton protocol”, has fuelled efforts to create a reproducible and immune-compatible source for new β cells. Human liver cells from the same patient as a source for new β cells represent a very attractive therapeutic option for developing a cell replacement therapy of diabetes with tremendous economic and societal benefits. The success of the “TheLiRep” PoC and associated intellectual property portfolio will allow to move forward the development of “cell-based medicines” for diabetes.
Diabetes mellitus represents a worldwide extremely important public health problem considering its high prevalence, the serious complications triggered by the disease, the associated rate of mortality and, not the least, the high economic and social costs. Despite the growing burden of diabetes, no cure has yet been found for the disease and the conventional treatments, based on exogenous insulin or oral agents, may control and delay but not prevent the disease complications. Thus, mortality and morbidity have steadily been increasing. Two major groups of diabetes have been defined: type 1 and type 2. Type 1 diabetes is an autoimmune disease that results in the destruction of the insulin-producing pancreatic β cells. It usually presents in childhood and patients require lifelong insulin. Type 2 diabetes, the most common form of the disease, is characterized by a combination of resistance to insulin action and inadequate compensatory insulin secretory response, leading to a decline in insulin production and later pancreatic β cell failure. The ability of cadaveric islet transplantation to restore euglycemia in patients with severe type 1 diabetes, known as the “Edmonton protocol”, has fuelled efforts to create a reproducible and immune-compatible source for new β cells. Human liver cells from the same patient as a source for new β cells represent a very attractive therapeutic option for developing a cell replacement therapy of diabetes with tremendous economic and societal benefits. The success of the “TheLiRep” PoC and associated intellectual property portfolio will allow to move forward the development of “cell-based medicines” for diabetes.