The Effect of the New Selective GLP-2 Agonist, Elsiglutide, On Irinotecan-Induced Diarrhoea and Mucositis in the Rat. (#20)
Introduction: Mucositis, a debilitating gastrointestinal (GI) side-effect of cancer treatment, affects cancer patients' quality of life and treatment regimens. Glucagon-like peptide-2 (GLP-2), a growth-promoting GI peptide, is a potential agent for mucositis treatment and prevention.
Objectives: We aim to test a longer-acting synthetic derivative of GLP-2 in a model of mucositis (Elsiglutide (Helsinn Healthcare, Switzerland)), which could improve GI damage and diarrhoea caused by chemotherapy.
Methods: A Dark Agouti rat model of irinotecan (IRI)-induced mucositis was used to characterise effects of Elsiglutide on IRI-induced diarrhoea, GI pathology, cell proliferation and inflammation. Animals were given 200mg/kg intraperitoneal IRI, followed by daily subcutaneous dosing of 0.9 or 1.8mg/kg Elsiglutide, then killed at 6, 72 or 120 hours post-chemotherapy (n=6). Sections of jejunum and ileum were taken for analysis.
Results: Elsiglutide treatment significantly ameliorated incidence of IRI-induced diarrhoea. It also significantly (p<0.05) increased small intestinal wet weight of IRI-treated rats receiving 0.9mg/kg Elsiglutide (4.3±0.5g at 72hrs, 8.6±0.3g at 120hrs) when compared with controls (3.2±0.09g at 72hrs, 6.4±0.5g at 120hrs). Small intestinal histology showed that villous blunting, crypt ablation and enterocyte disruption was improved in the jejunum of IRI-treated rats in combination with 0.09mg/kg Elsiglutide at both 6hrs and 72hrs. Plasma endotoxin levels showed a trend towards decreasing at 6hrs and 72hrs in response to Elsiglutide.
Conclusion: These preliminary results indicate that Elsiglutide can improve IRI-induced diarrhoea and damage from as early as 6hrs after treatment. Investigation and dose refinement of Elsiglutide is ongoing in order to provide further evidence of mucositis prevention and amelioration.