otable trends. The appearance of remitted animals in the A-83-01 biological activity groups treated with Tregitopes was promising. Interestingly, 12537482 within the 5 control groups combined there were 9 mice that rapidly progressed and required euthanasia in the first week of treatment as compared to 3 such mice in the combined treatment groups. 7) PGC-GLP-1 Glucagon-like peptide 1 is an intestinal hormone that increases insulin secretion in response to a meal, by a number of different mechanisms. GLP-1 has been approved for use in type 2 diabetes, based on its efficacy in helping reduce blood glucose. Published studies have also suggested that GLP-1 can promote beta cell replication in rodents. For these reasons, GLP-1 is an interesting molecule for the treatment of type 1 diabetes, but the native peptide has a very short half-life. The company PharmaIN has non-covalently coupled GLP-1 to a nanocarrier and proposed that this longer-lived compound be tested in the NOD T1D model. The PGC nanocarrier molecules significantly slows the digestion of GLP-1 by dipeptidylpeptidase-IV and decreases GLP-1 glomerular filtration, thus prolonging GLP-1’s half-life in the circulation. Preliminary data from the company suggested that PGC-GLP-1 given at 3mg/kg/week for 8 weeks starting at four weeks of age could reduce the incidence of T1D in the NOD so the hypothesis that PGC-GLP-1 could possibly promote diabetes reversal in newly onset diabetic NOD mice when used in combination with anti-CD3 was tested. We performed a 6 group, n=12 mice/group reversal study designed 9 Efficacy Testing in Rodent Models of T1D doi: 10.1371/journal.pone.0072989.g008 to detect a 35% increase in diabetes remission by PGC-GLP-1 in the treated groups as compared to the vehicle control. Animals with 7685384 confirmed diabetes were enrolled into the study. Groups were, PGC or PGC-GLP-1 coadministered with an immunomodulator or control F2 antibody. The number of mice exhibiting normoglycemia/total number of mice enrolled was as follows: Group 1 = 0/10; Group 2 = 6/12; Group 3 = 1/10; Group 4 = 8/12; Group 5 = 0/12; and Group 6 = 6/12. PGC-GLP-1 did not demonstrate efficacy at 1mg GLP-1/kg/ week either alone or in combination with anti-CD3 in this model. The remission frequency observed herein for anti-CD3 was very similar to that previously reported. Thus, we demonstrated that diabetes can be efficiently reversed in the NOD mouse 
within our facility, using a method which is well established in many laboratories. 10 Efficacy Testing in Rodent Models of T1D doi: 10.1371/journal.pone.0072989.g009 Discussion We report here the efforts of the NIDDK to coordinate voluntary standardized testing of different treatments for T1D that are under development by academic investigators and small companies, using rodent models of disease and carried out by an independent contract research laboratory. We used internally consistent methods, and attempted a thorough reporting of study results and procedures, following some of the principles outlined by Landis and colleagues for preclinical research. Our goals were to provide an opportunity to test novel compounds for possible therapeutic application in T1D. We used an open solicitation for ideas and compounds, and offered access to requestors whose agents were selected for study, to have input on the experimental design of studies, with the caveat that the studies had to be performed in the BRM contract laboratory using standard operating procedures whenever possible. Our goal was not to
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