Guselkumab and the Expanding Utility of Zebrafish Models in Ulcerative Colitis Research

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by persistent inflammation of the colon, mucosal ulceration which leads to disrupting the quality of life. Traditional therapies often introduced new risks including bradycardia, macular edema and other metabolic complications highlighting the need for new targeted interventions. Guselkumab, is a monoclonal antibody which was designed to block interleukin-22 (IL-22) driven inflammatory signaling, provides more precise controlling of intestinal inflammation and promoting mucosal healing.

A Comprehensive set of assays supported the development of guselkumab. Surface Plasmon Resonance (SPR) and Kinetic Exclusion Assay (KinExA) defined binding kinetics and antibody–cytokine affinity. Cytokine levels across inflammatory pathways evaluated using ELISA and H&E staining revealed the tissue remodeling, fibrosis and mucosal repair. Other biomarkers such as C-reactive protein (CRP) provided data on systemic inflammation and immunological response.

FDA approval was given due to better outcomes of clinical trials, particularly improvements in clinical remission, endoscopic healing, and mucosal function. Combined results showed that guselkumab not only reduces inflammation but also restores mucosal integrity which is considered essential for long-term UC control.

Expression levels of C Reactive Protein and TNF-α in Zebrafish UC Model, illustrating differential response patterns across various groups.

Zebrafish currently emerged as an invivo model for studying gut inflammation. Chemically induced colitis zebrafish models show epithelial damage and neutrophil infiltration, allows the assessment of therapeutic effects. Histological Imaging to visualize neutrophil and macrophage recruitment, key hallmarks of UC pathology. Intestinal permeability assays help to quantify epithelial barrier restoration and using qPCR for analyzing inflammatory markers (il22, tnfa, il1b) reveals rescue following treatment. Imaging also enables evaluation of epithelial regeneration, goblet cell recovery and reduction in oxidative stress within the gut.