Newer therapeutic targets in Inflammatory bowel disease

March 16, 2024

2,854 3 minutes read

Presented in 13th World Gastroenterology, IBD & Hepatology Conference in Holiday Inn Dubai, Al Barsha, UAE & Virtual from December 15-17, 2023.

Poster Name: Dr. Sreekanth Gaddam
Category: Poster presentation
Research interest: Gastroenterology
Biography: Dr Gaddam is a final year student of MSc Internal medicine from the University of Edinburgh, UK. He is presently working as a General Physician in Noor Al Ahli medical center, Al Ain, UAE.

Sreekanth Gaddam¹ and Vijayalaksmi Gudivada², ¹(General Physician, Noor Al Ahli medical center, Al Ain, UAE. Affiliation- The University of Edinburgh, UK), ²(Specialist Pathologist, Prime medical center, Dubai, UAE. Affiliation- JIPMER, Pondicherry, India).

Global Journal of Gastroenterology & Hepatology Research [GJGHR]
Visit Poster Presenter page: https://gastroenterology.universeconferences.com/speaker/sreekanth-gaddam/

Introduction:
Inflammatory bowel disease (IBD), a complex, se-vere, chronic inflammatory disorder affecting the ga-strointestinal tract, can fluctuate and resist standard therapy. IBD research, biomarker identification, pathophysiology and molecular mechanisms exploration have led to prospective therapy targets that can alter the disease’s early course. Exploring newer, more effective medicines that reduce flares, induce rapid remission, and improve care is important.1

Non-biologic medicines alleviate symptoms but do not modify disease progression. Biologics induce and maintain remission of both Crohn’s disease and ulcerative colitis.3 Drugs targeting different stages of disease process to halt the progression have been identified. Novel therapy targets include improving epithelial barrier function, inhibiting pro-inflammatory cytokinin, limiting inflammatory cell trafficking, and boosting regulatory T cell function.1

Immunopathogenesis of IBD:

Figure 1. Bani Ahluwalia, Luiza Moraes, Maria K.Magnusson &Lena Öhman

DC: dendritic cell; ILC: innate lymphoid cells; Th: T-helper cell; Treg cell: regulatory T cell; IL: interleukin; TNF: tumor necrosis factor; IFN: interferon; TGF-β: transforming growth factor- β; AB: antibody; CCR: chemokine receptor; MAdCAM-1: mucosal addressin cell adhesion molecule-1; α4β7: integrin; LP: lamina propria

IBD is characterized by altered effector T cells, elevated B cells and antibody production, and increased pro-inflammatory mediators.²

Figure (1) shows the major innate and adaptive immune cells implicated in IBD pathogenesis and the cytokines produced by respective cell subsets in the afflicted mucosa. Chronic inflammation results from cytokine activation and maintenance, as well as limited regulation of anti-inflammatory cytokines (IL-1- and TGF-β). Inflamed intestines boost Mad-CAM-1 expression, which recruits gut-specific T lymphocytes to the LP.²

Figure 2. Therapeutic targets for IBD

IL: interleukin; TNF: tumor necrosis factor: IL-6R: interleukin 6 receptor; TLR9: toll-like receptor 9; S1P: sphingosine-1-phosphate; Th: T-helper cell; Treg: regulatory T-cell; TGF-β: transforming growth factor-β: IFN: interferon

Newer Therapeutic targets: Currently, successful IBD treatments target TNF-α, including infliximab, adalimumab, certolizumab pegol, and golimumab. Vedolizumab, an α4β7 integrin blocker, affects gut T-cell homing. JAK inhibitor tofacitinib and IL-12/23 p40 blocker ustekinumab interrupt effector T cell differentiation. IL-23 p19 subunit inhibitor risankizumab and lymphocyte homing modulator ozanimod were recently approved. selective JAK inhibitor filgotinib and TLR9 agonist cobitolimod are nearing approval.² Upadacitinib, an FDA-approved JAK Kinase inhibitor, is another novel Ulcerative Colitis (UC) therapy. UC treatment with fecal microbiota transplantation is promising, but many issues remain.⁴

Conclusion: Newer, better, and safer IBD treatments are needed. Treat to target, early intervention, biomarker identification, personalization, and disease prevention are new therapy approaches. Novel medicines, microbiome consumption, and stem cells targeting disease pathways in IBD pathogenesis enable new therapeutic targets.

References:

Katsanos KH, Papadakis KA. Inflammatory Bowel Disease: Updates on Molecular Targets for Biologics. Gut Liver. 2017 Jul 15;11(4):455-463. doi: 10.5009/gnl16308. PMID: 28486793; PMCID: PMC5491079.
Ahluwalia B, Moraes L, Magnusson MK, Öhman L. Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scand J Gastroenterol. 2018 Apr;53(4):379-389. doi: 10.1080/00365521.2018.1447597. Epub 2018 Mar 9. PMID: 29523023.
Na SY, Moon W. Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease. Gut Liver. 2019 Nov 15;13(6):604-616. doi: 10.5009/gnl19019. PMID: 31195433; PMCID: PMC6860034.
Marsool MDM, Vora N, Marsool ADM, et al. Ulcerative colitis: Addressing the manifestations, the role of fecal microbiota transplantation as a novel treatment option and other therapeutic updates [published online ahead of print, 2023 Jun 24]. Dis Mon. 2023;101606. doi:10.1016/j.disamonth.2023.101606

Keywords: Inflammatory bowel disease (Crohn’s disease and ulcerative colitis), New therapeutics, Biologics