P3.05: Apraglutide Decreases Severity of Intestinal Damage From Acute Gastrointestinal Graft Versus Host Disease (GI-GvHD) Following Allogeneic Transplantation Without Impacting Engraftment
Bibliographic record
Abstract
Background: The GI tract is a primary tissue system damaged by GvHD, leading to a compromised mucosal barrier, mucosal protein loss, and nutrient/fluid absorption failure. Glucagon-like peptide-2 (GLP-2) has demonstrated intestinotrophic effects, enhanced barrier function, and decreased intestinal permeability. Apraglutide, a novel, long-acting synthetic GLP-2 analog, represents a potential regenerative approach to GI GvHD prevention and treatment. Using two mice models of GvHD, we assessed the effects of apraglutide on engraftment and GI protection following irradiation and allogeneic transplantation. Methods: In Study 1, total-body-irradiated (TBI) immunodeficient (NOG) mice (Day 0) were injected with human peripheral blood mononuclear cell (hPBMC; 3x107; Day 2) and treated with apraglutide 3.3 mg/kg or vehicle (Days -6 to 18). Engraftment rate was determined through CD45 expression (human vs. mouse) in blood, bone marrow, and spleen. In Study 2, TBI-induced intestinal damaged BALB/cJ mice received allogeneic transplantation from C57BL/6 strain and were treated with apraglutide (3.3 mg/kg) or vehicle (Days -9, -7, -5, -3 -1, +1, +3, +5, +7). Intestinal damage indicative of GvHD (histological changes, length, hemorrhage, inflammation), body weight, and survival were assessed. Results: In study 1, hPBMC were successfully engrafted. The engraftment rate in blood, spleen, and bone marrow was not affected by apraglutide (range 22.2-47.6% at D20 in blood). hCD45+ cell infiltration was observed in the intestinal wall with no difference between apraglutide vs. vehicle. In study 2, lymphocyte engraftment was successfully achieved in both apraglutide- and vehicle-treated mice. Weight loss and median survival were similar in both groups, but apraglutide-treated mice had significantly higher overall survival vs. vehicle on Day +9 (40% vs. 0%, respectively; p=0.0134). Post-mortem histological examination revealed less mucosal degenerative/inflammatory changes (villous atrophy, mononuclear/neutrophilic cell infiltrate in the lamina propria/intra-cryptal epithelium, crypt necrosis) in apraglutide-treated mice vs. vehicle. Mean colon length in the apraglutide group (8.6±0.35 cm) was comparable to mice that did not undergo irradiation or transplantation (9.6±0.33 cm), whereas a significant reduction was apparent in the vehicle group (7.19±0.10 cm; p <0.05). Conclusion: These results suggest that apraglutide treatment before allogeneic transplantation in immunodeficient mice does not affect engraftment rate. Furthermore, apraglutide showed a significant protective effect in TBI- and allogeneic-transplant-induced GvHD with reduced villi atrophy, less colon shortening, less severe intestinal damage, and showed a survival advantage. These findings support the beneficial role of apraglutide in reducing GI damage and limiting mortality from GvHD.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".