ABSTRACT
Type 1 diabetes mellitus (T1D), also called juvenile diabetes, is a chronic autoimmune disorder that precipitates in genetically susceptible individuals by environmental factors.1 The body’s own immune system attacks the β-cells in the islets of Langerhans of the pancreas, destroying or damaging them sufciently to reduce and eventually eliminate insulin production, leading to hyperglycemia. Since the discovery of “insulin replacement” in the early 1920s and its rst life-saving application in a patient with juvenile diabetes, the hope has lingered that a cure for the disease is within reach. Today, however, despite the many remaining challenges in the eld of T1D immunotherapy, hope is approaching reality. This chapter summarizes current protein-or cell-based therapeutics that are approved for clinical trials or are still in preclinical research. These therapies include endocrinologist approaches to increase β-cell mass and/or function, (non-)autoantigen-specic immune intervention, or
Abstract .................................................................................................................. 189 Preclinical Immunological Events in T1D ............................................................. 190 To Prevent or to Intervene, That’s the Question ..................................................... 190
Identication of Prediabetic Individuals ........................................................... 190 Preventive Trials ................................................................................................ 191
Failure between Bench and Bedside ...................................................................... 192 Role of the Patient History in the Success or Failure of Treatments................. 192 Inuence of Viral Infection on Type I Diabetes ................................................ 193
New-Onset T1D Trials ........................................................................................... 193 Replacing β-Cell Deciency in Recent-Onset T1D .......................................... 194 Antigen Non-Specic Intervention Trials in T1D ............................................. 194 Antigen-Specic Intervention Trials in T1D ..................................................... 197 Combination Intervention Trials in T1D ........................................................... 198 Cell-Based Tolerogenic Therapy ....................................................................... 199
Promising Bench-Side Therapeutics ......................................................................200 Conclusions ............................................................................................................202 References ..............................................................................................................202
combinations thereof. Last, a peek over the fence of preclinical research will provide insights in what might enter the pipeline of therapy development.
