VBP15, a Novel Anti-Inflammatory, is Effective at Reducing the Severity of Murine Experimental Autoimmune Encephalomyelitis

Abstract

Multiple sclerosis is a chronic disease of the central nervous system characterized by an autoimmune inflammatory reaction that leads to axonal demyelination and tissue damage. Glucocorticoids, such as prednisolone, are effective in the treatment of multiple sclerosis in large part due to their ability to inhibit pro-inflammatory pathways (e.g., NFκB). However, despite their effectiveness, long-term treatment is limited by adverse side effects. VBP15 is a recently described compound synthesized based on the lazeroid steroidal backbone that shows activity in acute and chronic inflammatory conditions, yet displays a much-reduced side effect profile compared to traditional glucocorticoids. The purpose of this study was to determine the effectiveness of VBP15 in inhibiting inflammation and disease progression in experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of multiple sclerosis. Our data show that VBP15 is effective at reducing both disease onset and severity. In parallel studies, we observed that VBP15 was able to inhibit the production of NFκB-regulated pro-inflammatory transcripts in human macrophages. Furthermore, treatment with prednisolone—but not VBP15—increased expression of genes associated with bone loss and muscle atrophy, suggesting lack of side effects of VBP15. These findings suggest that VBP15 may represent a potentially safer alternative to traditional glucocorticoids in the treatment of multiple sclerosis and other inflammatory diseases.

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Abbreviations

EAE:

Experimental autoimmune encephalomyelitis

MS:

Multiple sclerosis

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Acknowledgments

This work was partially supported by the National Centers for Medical Rehabilitation Research, Molecular and Functional Outcome Measures in Rehabilitation Medicine Core, NIH NCMRR/NINDS 2R24HD050846-06.

Conflict of interest

Jesse M. Damsker is an employee of ReveraGen BioPharma and has stock options. Erica K. M. Reeves is an employee of ReveraGen BioPharma and has stock options. John M. McCall is an employee of PharMac LLC and has founder shares and a board membership with ReveraGen BioPharma. Eric P. Hoffman has founder shares and a board membership with ReveraGen BioPharma. Edward M. Connor has stock options and a board membership with ReveraGen BioPharma. Finally, Kanneboyina Nagaraju has founder shares and a board membership with ReveraGen BioPharma.

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Correspondence to Jesse M. Damsker.

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Dillingham, B.C., Knoblach, S.M., Many, G.M. et al. VBP15, a Novel Anti-Inflammatory, is Effective at Reducing the Severity of Murine Experimental Autoimmune Encephalomyelitis. Cell Mol Neurobiol 35, 377–387 (2015). https://doi.org/10.1007/s10571-014-0133-y

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Keywords

  • Multiple sclerosis
  • Glucocorticoids
  • Inflammation
  • Autoimmunity