Ex Vivo Comparison Of Combination Versus Single Therapeutic Pathway Inhibition In Human Intestinal Mucosa From Patients With Inflammatory Bowel Disease

The purpose of this study is to evaluate whether simultaneously targeting three inflammatory pathways (TL1A, IL-23, and α4β7) produces a stronger anti-inflammatory effect in intestinal tissue from patients with Inflammatory Bowel Disease (IBD) compared with targeting individual pathways. The study aims to investigate whether this combined approach may help overcome limitations associated with single-pathway inhibition. This is a single-center, interventional ex vivo study conducted at IRCCS Ospedale San Raffaele. The study includes 30 participants divided into three cohorts: 10 patients with Ulcerative Colitis, 10 patients with Crohn's Disease, and 10 non-IBD control participants. Participant involvement is limited to a single day and is integrated into a clinically indicated, routinely scheduled colonoscopy and routine phlebotomy. During the scheduled colonoscopy, 8 additional mucosal biopsies are collected for research purposes, together with an additional 2 mL blood sample. No additional endoscopic procedure or separate study visit is required. No investigational drug or treatment is administered directly to participants. The collected intestinal biopsies are instead treated ex vivo in the laboratory with ATTO-1091, individual pathway inhibitors, or control conditions for 16 hours. Biological and molecular responses are evaluated using laboratory techniques including ELISA and RNA sequencing to assess inflammatory markers and gene expression. Laboratory personnel performing molecular and transcriptomic analyses are blinded to participants' clinical profiles until final data analysis.