Gm-0111, A Modified Glycosaminoglycan, to Prevent Radiation-Induced Mucositis.

e20688 Background: Mucositis is an inflammatory disease that frequently develops during radiation and chemotherapy posing serious challenges to patients undergoing cancer treatments. Currently available treatments for mucositis largely rely on symptomatic relief. GM-0111 is a modified glycosaminoglycan that blocks various innate immune molecules such as TLRs and selectins. GM-0111 also broadly suppresses bacterial growth present in the oral cavity. We investigated whether these anti-inflammatory and anti-bacterial effects of GM-0111 could be exploited to prevent radiation-induced oral mucositis by testing in vitro and in vivo radiation-induced mucositis models. Methods: (1) In vitro studies: human oral epithelial cells (HOEPs) and mouse macrophage cells were treated with GM-0111 and irradiated with x-rays (10 Gy), and cell death was determined by flow cytometry assay using Annexin V/7-AAD binding to cells. (2) In vivo studies: BDF1 mice were subcutaneously treated with either saline or 30 mg/kg of GM-0111 once daily (Days -2 to 7). On Day 0, mice were irradiated with single dose X-rays at 20 Gy. On Day 8, we harvested tongue samples and determined the degree of inflammation by gross and histological examinations as well as detection of myeloperoxidase (MPO) in the tissues. Results: GM-0111 at 100 µg/mL significantly reduced x-ray-induced cell death in both HOEPs and macrophage cells. Mice treated with GM-0111 showed markedly reduced signs of inflammation in the tongue with decreased infiltration of polymorphonuclear leukocytes in the mucosa, thicker epithelial layer, and normal mucous glandular morphology than the saline treated group. MPO analysis confirmed our histological observations with significantly (p < 0.01) lower concentrations of MPO in GM-0111 treatment groups compared to vehicle treated groups (saline/20 Gy 206 ± 77 vs. GM-0111/20Gy 104 ± 27 mU/mg protein; normal 62 ± 23 mU/mg protein). Conclusions: GM-0111 reduces radiation-induced cell death and inflammation in the tongue and can potentially reduce clinical signs of oral mucositis that frequently occur during radiotherapy in cancer patients.