ents for efficacy in reversing or preventing T1D in rodents. NIDDK issued a Request for Information that provided a pathway for scientists to propose agents for testing. Proposed agents were reviewed for program applicability and translational potential by an independent review committee. In this initial stage of the testing program, we emphasized testing of agents for which there was some prior data for efficacy, albeit incomplete or preliminary, reported in the literature or communicated by the agent provider. In Saracatinib supplier addition, we selected agents that were known to react with both rodent and human targets, with similar biological responses and functional pathways, with the expectation that such agents could be more directly translated to the clinic. For a positive control, we used anti-CD3 which is a mouse-specific equivalent of the human therapeutic. Meanwhile, BRM established significantly improved insulin therapy methods for rat and mouse models of spontaneous autoimmune diabetes. These methods provide improved glycemic control in the animals as soon as possible after disease onset, to better model human therapy and to allow rigorous testing of agents for diabetes reversal. Materials and Methods Randomization Animals were not randomized into treatment groups; instead we used a staggered and fixed enrollment onto study, 2578618 i.e., 1st diabetic animal into Group 1, 2nd diabetic animal into Group 2, etc. Data was not collected randomly, but according to a predetermined schedule. Blinding: 1) Allocation concealment: Staff were not blinded as to which group would be enrolled next since a fixed staggered enrollment procedure was used. 2) Assessment of outcomes: Staff were not blinded as to the treatment groups of animals when making blood glucose measurements and general health assessments. Staff and subcontractors were blinded to treatment group when reading slides during histological assessments. 3) Interim data analysis: interim analyses were performed, but these did not alter the number of animals in the study, i.e enrollment was pre-determined and was not reduced or increased as a result of interim analyses. Sample size estimation We used either an independent biostatistician or Statmate to calculate sample sizes before each study. The analyses were predetermined and not adjusted at the study end. Data handling Data collection was protocol specified and all data was analyzed. Outliers were not excluded. Primary end points were protocol-specified and finalized prior to initiation of each study. Attrition was reported in the study figures, tables, and reports. Pseudo replicates were not 7679030 performed. Significant protocol or procedural deviations were documented and reported. In some circumstances, we performed a few studies with different designs to confirm or expand upon earlier results. 2 Efficacy Testing in Rodent Models of T1D Test Articles and Formulation Cyclosporin A and 20% intralipid were purchased from Sigma, formulated once weekly and stored at 2-8C. DT22669 was provided by the manufacturer, stored at 2-8C, and formulated in sterile 0.9% sodium chloride. Aralast NP was purchased from the manufacturer, and stored at 2-8C until formulated per manufacturer’s instructions within three hours of administration. ISO-092 was provided by the Feinstein Institute for 
Medical Research, resuspended in vehicle and stored ambient during the course of the study. Celastrol was purchased from the manufacturer in single-use vials and stored at 2-8C until
