PBI-4547 Prevents Progression of Prediabetic Condition to Type 1 Diabetes in NOD Mice
Bibliographic record
Abstract
Introduction: PBI-4547 is a novel orally active compound that is being developed for potential clinical use in patients suffering from metabolic and inflammatory/fibrosis-related diseases. This study examined the effect of PBI-4547 in NOD mice, a model of type 1 diabetes. Our objective was to demonstrate the efficacy of PBI-4547 to stop the progression of diabetes in mice exhibiting prediabetic glucose escalation. Methods: NOD/ShiLtJ female mice (8 weeks of age) were followed up to the appearance of the first sign of hyperglycemia (three consecutive weeks of glucose increase (over 7 mmol/l). Once identified as prediabetic, mice were randomly allocated to control (receiving vehicle (water)) or PBI-4547 (25 mg/kg/day) groups for treatment by daily gastric gavage for 8 to 12 weeks. Results: Mice treated with vehicle (n=9) evolved to a moderate to severe diabetic condition (glucose levels 11.7-37 mmol/l). Most of these vehicle-treated mice (6/9) survived only a few weeks after the onset of the prediabetic condition. At the opposite, NOD mice treated with PBI-4547 all showed a reversal of their hyperglycemia and none of the observed animals (n=12) evolved to a chronic hyperglycemia (over 11 mmol/l). Survival was also significantly improved in the group treated with PBI-4547 with 8 of 12 mice surviving more than 10 weeks after the onset of treatment. Analysis of insulinemia showed a significant difference between both groups. Immunohistological analysis of pancreas recovered at euthanasia revealed a significant reduction in islet inflammatory cell infiltration. Moreover, NOD mice treated with PBI-4547 maintained normoglycemia despite a reduced number of islets. In fact, PBI-4547 reduced by 30% the number of severely damaged islets. Conclusions: These data suggest that PBI-4547 could preclude the evolution of diabetes in a type 1 model. Disclosure F.A. Leblond: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. K. Hince: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. F. Sarra-Bournet: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. W. Gagnon: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. M. Tremblay: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. M. Cloutier: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. S. Létourneau: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. J. Simard: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. M. Leduc: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. B. Grouix: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. P. Laurin: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc.. Board Member; Self; Prometic Life Sciences Inc. L. Gagnon: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc..
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".