Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis

Lindemann A, Roth D, Koop K, Neufert C, Zundler S, Atreya R, Neurath M, Leppkes M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Medicine Frontiers Media

Book Volume: 10

Article Number: 1177450

DOI: 10.3389/fmed.2023.1177450

Abstract

Background and aims: Acute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel calcineurin inhibitor, voclosporin, has been approved for the treatment of lupus nephritis with no need for therapeutic drug monitoring and an improved long-term safety profile. However, the therapeutic effect of voclosporin in acute severe steroid-refractory ulcerative colitis is still uncertain. We aimed to assess the therapeutic potential of voclosporin to ameliorate inflammation in an experimental model of colitis. Methods: We used the dextran sodium sulfate-induced model of colitis in C57BL/6 J wildtype mice treated with either cyclosporine A, voclosporin or solvent control. We employed endoscopy, histochemistry, immunofluorescence, bead-based multiplex immunoassays and flow cytometry to study the therapeutic effect of calcineurin inhibitors in a preventive setting. Results: Acute colitis was induced by dextran sodium sulfate characterized by weight loss, diarrhea, mucosal erosions and rectal bleeding. Both cyclosporine A and voclosporin strongly ameliorated the course of disease and reduced colitis severity in a similar manner. Conclusion: Voclosporin was identified as biologically effective in a preclinical model of colitis and may be a potential therapeutic option in treating acute severe steroid-refractory ulcerative colitis.

Authors with CRIS profile

Aylin Lindemann Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Dominik Roth Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kristina Koop Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Clemens Neufert Medizinische Fakultät Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Moritz Leppkes Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung (IZKF)

Related research project(s)

A097: Mucosal healing in IBD: deciphering the role of STAT3 activation in intestinal mesenchymal cell populations July 1, 2023 - Dec. 31, 2025

How to cite

APA:

Lindemann, A., Roth, D., Koop, K., Neufert, C., Zundler, S., Atreya, R.,... Leppkes, M. (2023). Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis. Frontiers in Medicine, 10. https://doi.org/10.3389/fmed.2023.1177450

MLA:

Lindemann, Aylin, et al. "Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis." Frontiers in Medicine 10 (2023).

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