Inflammatory Bowel Disease (IBD), encompassing Crohn’s disease and ulcerative colitis, represents a global health crisis characterized by rising incidence, substantial socio-economic burdens and an elevated risk of colorectal cancer or other co-morbidities. While biologics like anti-TNF transformed care, they remain inadequate for many; with approximately 30% of patients failing to respond to induction therapy, and another 40% relapsing within a year. This therapeutic gap necessitates the discovery of novel pathways that control intestinal inflammation.
Emerging evidence reveals a provocative pathophysiological overlap between IBD and Parkinson’s disease (PD). This includes a well-described deficiency in dopamine as a hallmark of PD, while recent data shows dopamine levels are also significantly reduced in the inflamed intestine of both human IBD patients and associated animal models.
Despite this knowledge, the cellular & molecular pathways regulating dopamine production in the gut, as well as the importance to tissue health versus chronic inflammation, remains poorly defined. Here we build on new and unexpected preliminary data revealing a novel cellular source of dopamine in the gut that is necessary to restrain chronic intestinal inflammation. In this proposal, we will define the role, regulation and therapeutic potential of this axis across pre-clinical animal models and in human IBD.
