Advancing drug discovery for Inflammatory bowel diseases through human intestinal organoid-based models.

MANUEL BRAGA NETO, , ASSISTANT PROFESSOR, CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE AT CASE WESTERN RESERVE UNIVERSITY, DEPARTMENT OF GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION, DIGESTIVE DISEASES AND SURGERY INSTITUTE CLEVELAND CLINIC, CLEVELAND, OH, USA INTRODUCTION Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory conditions that affect millions of patients worldwide. Despite recent advances, the available IBD drugs targeting the immune system have limited efficacy, and disease recurrence is common. AREAS COVERED In this review, the authors describe reported applications of human intestinal organoids to understand the mechanisms of actions and predict patient response to current IBD therapies. Furthermore, they also outline the potential of human intestinal organoid-based technologies to accelerate drug discovery in IBD and propose a framework to bridge discoveries from the bench to the bedside. EXPERT OPINION The lag in the development of novel IBD therapies reflects the complex nature of the disease and our poor understanding of its pathogenesis. The future breakthrough in understanding IBD and developing novel IBD drugs require development and adaptation of novel disease-relevant experimental models, including organoid-based models, to evaluate the efficiency and accurately predict response to therapy. Indeed, presently the utilization of intestinal organoids in the IBD field has been limited and were not used in the development of any of the currently available therapies, including biologics (anti-TNF, anti-12/IL23, anti-α4β7) and small molecules. The authors affirm that a stepwise approach would help accelerate future organoid-based drug discovery efforts.