New therapeutic approaches for type 1 diabetes: Disease-modifying therapies

Abstract

It has been 100 years since the first successful clinical use of insulin, yet it remains the only treatment option for type 1 diabetes mellitus (T1DM) patients. Advances in diabetes care, such as insulin analogue therapies and new devices, including continuous glucose monitoring with continuous subcutaneous insulin infusion have improved the quality of life of patients but have no impact on the pathogenesis of the disease. They do not eliminate long-term complications and require several lifestyle sacrifices. A more ideal future therapy for T1DM, instead of supplementing the insufficient hormone production (a consequence of β-cell destruction), would also aim to stop or slow down the destructive autoimmune process. The discovery of the autoimmune nature of type 1 diabetes mellitus has presented several targets by which disease progression may be altered. The goal of disease-modifying therapies is to target autoimmune mechanisms and prevent β-cell destruction. T1DM patients with better β-cell function have better glycemic control, reduced incidence of long-term complications and hypoglycemic episodes. Unfortunately, at the time symptomatic T1DM is diagnosed, most of the insulin secreting β cells are usually lost. Therefore, to maximize the salvageable β-cell mass by disease-modifying therapies, detecting autoimmune markers in an early, optimally presymptomatic phase of T1DM is of great importance. Disease-modifying therapies, such as immuno- and regenerative therapies are expected to take a relevant place in diabetology. The aim of this article was to provide a brief insight into the pathogenesis and course of T1DM and present the current state of disease-modifying therapeutic interventions that may impact future diabetes treatment.

Teplizumab – preventative approaches to type 1 diabetes mellitus

“…Teplizumab is a humanised monoclonal antibody that binds to CD3 (cluster of differentiation 3) cell surface antigens on T-lymphocytes and delays the onset of stage 3 T1DM in adults and children aged over eight years with stage 2 T1DM. 9 It is administered once-daily by intravenous infusion over 14 consecutive days. 10 The mechanism of action is not fully understood but may involve partial agonistic signalling with the development of anergy and deactivation of pancreatic β-cell autoreactive effector CD8+ T-lymphocytes, effectively turning off the autoimmune destruction of insulin producing pancreatic β-cells.…”

“…Teplizumab is a humanised monoclonal antibody that binds to CD3 (cluster of differentiation 3) cell surface antigens on T‐lymphocytes and delays the onset of stage 3 T1DM in adults and children aged over eight years with stage 2 T1DM 9 . It is administered once‐daily by intravenous infusion over 14 consecutive days 10 …”

Mesenchymal Stem Cells from Mouse Hair Follicles Inhibit the Development of Type 1 Diabetes

“…MSCs possess anti-inflammatory, anti-apoptotic, anti-tumorigenic, anti-fibrotic, neuroprotective, and chemo-attractive qualities and immense therapeutic potential for tissue repair and regeneration [ 13 ]. Accordingly, MSCs have been shown to be protective in treatments of autoimmune diseases [ 14 ], such as T1D, and have been abundantly assessed in animal models [ 15 ]. Their immunomodulatory properties have primarily been identified as the inhibition of pro-inflammatory immune cells and stimulation of Treg [ 15 ].…”

“…Accordingly, MSCs have been shown to be protective in treatments of autoimmune diseases [ 14 ], such as T1D, and have been abundantly assessed in animal models [ 15 ]. Their immunomodulatory properties have primarily been identified as the inhibition of pro-inflammatory immune cells and stimulation of Treg [ 15 ]. For example, human adipose-derived MSCs decreased the incidence of T1D in NOD mice by reducing the accumulation of T cells and macrophages in pancreatic islets, consequently increasing the insulin content and the size of the preserved islet beta cell area [ 16 ].…”

Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus

“…Currently, various cytokines and antibodies face the challenge of transportation to the target sites. Another limitation is that continuous immunosuppressive effects cannot be induced, leading to an off-target effect [ 17 ]. Hence, one of the core purposes of developing novel delivery strategies for immunotherapeutic agents is to achieve a targeted and controlled release [ 7 ].…”