Many studies have focused on clinical intervention therapies for autoimmune T1D, both during the evolution of the disease and at disease onset. The therapeutic objective, before disease onset, is to inhibit the immune destruction of pancreatic beta cells and thereby delay or prevent clinical disease. When disease onset has already occurred, the goal is to halt the destruction of the remaining beta cells, which may allow residual beta cells to recover function, thereby decreasing the severity of clinical signs and slowing the progression of the disease. An important aspect of setting up clinical trials for potential therapeutics, of course, is to accurately identify individuals at risk for T1D.
Potential therapies investigated in large clinical trials have first been found to be effective in animal models of autoimmune diabetes, as well as in small cohorts of human volunteers. Based on this data, some of the earliest large-scale studies were undertaken to investigate the therapeutic value of the B vitamin, nicotinamide, as well as both oral and parenteral insulin. Unfortunately, even though the initial pilot studies showed promise, none of these treatments proved to be effective in large-scale human trials28
Additional studies are currently focused on newborns with genetic risk factors for T1D. One such study is investigating whether the frequency of T1D can be reduced by preventing exposure to cow milk protein during early life24
. A second pilot study is examining the effectiveness of the omega-3-fatty acid, docosahexaenoic acid (DHA), in delaying or preventing diabetes. Moreover, several agents are being tested in patients with new onset T1D, including immunomodulatory therapies such as the p277 peptide from heat shock protein 60, anti-CD3 and anti-IL2-receptor monoclonal antibodies, and a GAD vaccine28
. In each case, initial promising results must await longer-term and larger-scale studies to validate their effectiveness.
Overall, many of the earliest and most promising potential therapeutics to slow the progression of T1D have proven disappointing. Although there has been progress in implementing studies designed to arrest or delay disease progression, there remains a real need to develop new and effective clinical therapies. Careful elucidation of molecular mechanisms involved in the pathogenesis of induced diabetes in animal models should facilitate this need. For example, as chloroquine was shown to inhibit TLR9 signaling and reduce the incidence of diabetes in KRV infected BBDR rats, this agent would represent a promising potential therapeutic for human T1D (). In addition, evidence from David Baltimore's laboratory has demonstrated a role for specific microRNAs (miRNA-155) in regulation of the inflammatory response29
. Manipulation of this miRNA may provide yet another means to ameliorate or prevent T1D (). These and other cutting-edge data gathered and assimilated from a large body of clinical and laboratory research should provide additional innovative treatments for human diabetes.