GLS-1027 as an Adjunct Treatment for Canine Inflammatory Bowel Disease
Principal Investigator: Jennifer Prieto
Co-PI: John Loftus
DESCRIPTION (provided by applicant):
GLS-1027 is an isoxazoline compound with immunomodulatory functions that include inhibiting Th17 mediated inflammation. In rodent models, GLS-1027 has been shown to modulate inflammation in autoimmune and inflammatory diseases, including uveitis, carrageenan-induced pleuritis, collagen-induced arthritis, systemic lupus erythematosus, and inflammatory colitis. In people, GLS-1027 is being evaluated as an adjunct therapy for the treatment of COVID-19. The immunomodulatory properties also make GLS-1027 a promising adjunct treatment in veterinary medicine, and clinical trials treating the immune-mediated disease idiopathic anterior uveitis are currently underway. Another potential application of GLS- 1027 in veterinary medicine is treating canine inflammatory bowel disease (IBD). The proposed study will test the treatment response of GLS-1027 in dogs with inflammatory bowel disease. The presumptive diagnosis of IBD will be established based on consistent clinical history, clinicopathologic data, and exclusion of hormonal, infectious, and neoplastic disease. This study includes two arms of testing to broadly assess the impact of GLS-1027 on immune function, and the clinical response of dogs with IBD: (1) We will measure the clinical response with GLS-1027 based on the chronic enteropathy clinical activity index and biochemical markers of gastrointestinal health (albumin, cholesterol) and inflammation (CRP, neutrophil-to-lymphocyte ratio [NLR]); (2) We will measure the proliferative response of mitogen-stimulated T cells producing the pro-inflammatory cytokine IL-17 ex vivo with optimized canine-specific EliSpot assays. We hypothesize that the GLS-1027 will modulate the inflammatory immune response and improve clinical signs in dogs with inflammatory bowel disease.