Inhibition of Interleukin-17 in Inflammatory Bowel Disease and Efficacy in Systemic Lupus Erythematosus Demonstrated
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A manuscript entitled '4SC-101, a Novel Immunosuppressive Drug,
Inhibits IL-17 and Attenuates Colitis in Two Murine Models of Inflammatory
Bowel Disease' has been published in Inflammatory Bowel Diseases, whilst a
comprehensive set of pre-clinical data in a systemic lupus erythematosus
(SLE) model has been released in the American Journal of Pathology under
the title '4SC-101, a novel small molecule dihydroorotate dehydrogenase
inhibitor, suppresses systemic lupus erythematosus in MRL-(Fas)lpr mice'.
The publication in Inflammatory Bowel Diseases is the result of a
collaboration with Prof. Leo R. Fitzpatrick, Department of Pharmacology,
Penn State College of Medicine, USA. Vidofludimus was demonstrated to
effectively improve both chronic and acute inflammatory bowel disease in
mice and to significantly inhibit the production of the pro-inflammatory
cytokine Interleukin-17 (IL-17) both in vitro and in vivo. Since IL-17
inhibition is independent from lymphocyte proliferation and other
signalling molecules such as TNF-?, IL-1? and IL-6 are not affected,
vidofludimus is assumed to block IL-17 production by a highly specific
mechanism which will be evaluated further in this collaboration.
In the American Journal of Pathology publication, the results of a collaboration with Prof. Hans-Joachim Anders, Medizinische Poliklinik Innenstadt, University of Munich, Germany, were published. In this in vitro and in vivo study, vidofludimus was demonstrated to be as effective as the standard therapy high dose cyclophosphamide (CYC) in controlling SLE without causing myelosuppression which is frequently seen with CYC. Vidofludimus was as effective as CYC in depleting spleen autoreactive T cells, B cells and plasma cells as well as the respective DNA and RNA serum auto-antibodies. This was associated with a comparable amelioration of renal, dermal and pulmonary SLE manifestations of MRL(Fas)lpr mice. However, even the highest dose of vidofludimus had no effect on bone marrow neutrophil counts which were significantly reduced in CYC-treated mice.
Dr Bernd Hentsch, Chief Development Officer of 4SC, commented: 'We are very excited about the progress we have made in our academic collaborations
which we pursue in parallel to our current clinical development program for
vidofludimus in rheumatoid arthritis and inflammatory bowel disease. These
excellent scientific results substantiate the positioning of vidofludimus
as a novel and broadly applicable anti-inflammatory drug which through its
dual mechanism of action inhibits cell proliferation and the cytokine
IL-17.'
References
- Fitzpatrick LR, Deml L, Hofmann C, Small JS, Groeppel M, Hamm S,
Lemstra S, Leban J, Ammendola A. 4SC-101, a novel immunosuppressive
drug, inhibits IL-17 and attenuates colitis in two murine models of
inflammatory bowel disease. Inflammatory Bowel Diseases 2010. Published
electronically on March 22, 2010.
- Onkar P. Kulkarni, Sufyan G. Sayyed, Claudia Kantner, Mi Ryu, Max
Schnurr, Miklós Sárdy, Johann Leban, Ruediger Jankowsky, Aldo
Ammendola, Robert Doblhofer, and Hans-Joachim Anders. 4SC-101, A Novel
Small Molecule Dihydroorotate Dehydrogenase Inhibitor, Suppresses
Systemic Lupus Erythematosus in MRL-(Fas)lpr Mice. American Journal of
Pathology 2010. Published electronically on April 22, 2010.
