Abstract: Recent efforts to ameliorate type 1 diabetes have largely failed to produce long term benefits in terms of insulin independence or even preservation of beta cell function. That said, past efforts have largely focused on the use of single immunotherapies. Our group has long proposed the need to approach type 1 diabetes intervention and prevention using a combination therapy approach. Efforts in Brazil, led by Voltarelli et al., have demonstrated that aggressive combination immunotherapy may indeed be capable of inducing both a short term remission and a long term preservation of beta cell function. However, due the risks associated with such an approach (non-myeloablative autotransplantation), our group has focused on dissecting the “Brazilian protocol” with the ultimate goal of generating an equally efficacious but lower risk, “Brazil-lite” approach.
Towards that end, we have performed a number of animal studies which have identified the potential for low dose Thymoglobulin combined with Neulasta to durably reverse NOD mice with established diabetes. In order to translate these findings to potential patient care, we have performed (1) a safety study of Neulasta monotherapy in patients with type 1 diabetes and (2) a pilot study of low dose Thymoglobulin and Neulasta in patients with established type 1 diabetes (> 4 months duration). This presentation will review the apparent mechanistic differences between our GCSF monotherapy study, the ongoing low dose ATG/GCSF trial, and the recently published START trial (high dose ATG monotherapy). In addition, we will provide a framework for our planned TrialNet study of ATG/GCSF vs ATG vs placebo in patients with new onset type 1 diabetes.