VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects
Article first published online: 9 SEP 2013
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 10, pages 1569–1585, October 2013
How to Cite
Heier, C. R., Damsker, J. M., Yu, Q., Dillingham, B. C., Huynh, T., Van der Meulen, J. H., Sali, A., Miller, B. K., Phadke, A., Scheffer, L., Quinn, J., Tatem, K., Jordan, S., Dadgar, S., Rodriguez, O. C., Albanese, C., Calhoun, M., Gordish-Dressman, H., Jaiswal, J. K., Connor, E. M., McCall, J. M., Hoffman, E. P., Reeves, E. K. M. and Nagaraju, K. (2013), VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med, 5: 1569–1585. doi: 10.1002/emmm.201302621
- Issue published online: 2 OCT 2013
- Article first published online: 9 SEP 2013
- Manuscript Accepted: 2 AUG 2013
- Manuscript Revised: 30 JUL 2013
- Manuscript Received: 8 FEB 2013
- United States Department of Defense CDMRP. Grant Numbers: W81XWH-05-1-0616, W81XWH-09-1-0218, W81XWH-11-1-0754
- Foundation to Eradicate Duchenne, the Muscular Dystrophy Association USA
- National Institutes of Health. Grant Numbers: R01-AR050478, 1U54HD053177-01A1
- Wellstone Muscular Dystrophy Center. Grant Number: RO1AR055686
- NIH. Grant Number: P50AR060836
- Center of Research Translation. Grant Number: 2R24HD050846-06
- Intellectual and Developmental Disabilities Research Center. Grant Number: P30HD040677
- Genetics and Genomics of Muscle. Grant Number: 5T32AR056993-02
- NIH. Grant Number: K26OD011171
- US Department of Defense. Grant Numbers: W81XWH-05-1-0659, W81XWH-11-1-0782
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Figure S1. Further in vivo efficacy data from the pre-symptomatic mdx trial. (A) The drop in force for EDL muscle after 10 lengthening contractions ex vivo showed a significant reduction upon VBP15 treatment at 15 mg/kg. (B and C) Live-animal imaging of cathepsin protease activity via ProSense680 shows reduced inflammatory disease in the forelimbs of VBP15-treated mdx mice (B) images; C quantitation of fluorescence; n ≥ 6 mice/group). (D) H&E stained histology of diaphragm muscle shows a decrease in calcified myofibres upon VBP15 treatment. In diaphragm sections, calcified fibres were present in a majority (5 of 6) of vehicle mdx mice. VBP15 treated mice showed reduced calcification upon quantitation, with only 1–2 mice per group exhibiting any calcified fibres (n = 6 mice/group). (*p < 0.05, n = 10 mice/group).
Figure S2. Further in vivo immunology and side effect data from the pre-symptomatic mdx trial. (A) Spleen to body mass ratios were measured upon trial conclusion (8 weeks). Note, mdx spleens were enlarged in comparison to WT, while VBP15 normalized spleen size toward WT levels and prednisolone reduced spleen size such that it was lower than WT. (B) Peripheral blood leucocyte counts were assayed at trial conclusion. (C–E) Histological analysis of gastrocnemii muscle shows increased skeletal muscle degeneration and fibrosis in prednisolone-treated mice, but not VBP15 mice. A significant increase in degenerating fibres (C) was present in prednisolone treated gastrocnemii, quantified in H&E stained sections. Digital quantitation (D) of sirius red staining shows a significant increase in skeletal muscle fibrosis in prednisolone treated mice. Representative images of sirius red staining are provided (E), to the right of the panel is a higher magnification image from the area outlined in box. (n ≥ 12 mice/group for (A and B); n = 6 mice/group for (C and D); *p < 0.05, **p < 0.05, ***p < 0.05).
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