PROJECT: JTC 2025 - Pain: CURE CVP

Chronic Visceral Pain (CVP) originates from our internal organs, is debilitating and significantly reduces the quality of life for ~20% of Europeans and Australians. A leading cause of CVP is Irritable Bowel Syndrome (IBS), an insidious condition characterised by CVP, altered gut motility and co-morbidities of bladder dysfunction, anxiety, depression and fibromyalgia. Changes along the microbiome-gut-brain axis contribute to the pathogenesis of IBS and its co-morbidities. We have developed a novel gut-stable oxytocin receptor agonist (half-life >24 hrs) that reduces CVP in animal models after a single oral dose. This project aims to determine the efficacy of chronic oral dosing and the analgesic mechanisms of action underpinning oxytocin receptor activation. Using human patient-derived organoids and biospecimens with humanised mouse models and clinically relevant pre-clinical models, we will determine how chronic oral dosing of our gut-stable oxytocin agonist 'OTR-26' restores normal gut physiology (microbiome, bacterial metabolites and epithelial function) and reverses neuroplasticity along the microbiome-gut-brain axis (sensory afferents, spinal cord dorsal horn and brain) to reduce CVP and IBS co-morbidities. Positive findings from this study would provide a new and highly promising pathway towards developing a novel oral therapy for the treatment of CVP in IBS patients, thereby addressing a significant unmet global medical need.