Silencing Nogo-A promotes functional recovery in demyelinating disease
Article first published online: 7 DEC 2009
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 67, Issue 4, pages 498–507, April 2010
How to Cite
Yang, Y., Liu, Y., Wei, P., Peng, H., Winger, R., Hussain, R. Z., Ben, L.-H., Cravens, P. D., Gocke, A. R., Puttaparthi, K., Racke, M. K., McTigue, D. M. and Lovett-Racke, A. E. (2010), Silencing Nogo-A promotes functional recovery in demyelinating disease. Ann Neurol., 67: 498–507. doi: 10.1002/ana.21935
- Issue published online: 26 APR 2010
- Article first published online: 7 DEC 2009
- Accepted manuscript online: 7 DEC 2009 12:00AM EST
- Manuscript Accepted: 20 NOV 2009
- Manuscript Revised: 6 OCT 2009
- Manuscript Received: 19 MAR 2009
- National Multiple Sclerosis Society. Grant Numbers: PP1028, JF2116, RG3812
- NINDS. Grant Number: K24 NS044250-01
- Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society
To determine if suppressing Nogo-A, an axonal inhibitory protein, will promote functional recovery in a murine model of multiple sclerosis (MS).
A small interfering RNA was developed to specifically suppress Nogo-A (siRNA-NogoA). The siRNA-NogoA silencing effect was evaluated in vitro and in vivo via immunohistochemistry. The siRNA was administered intravenously in 2 models of experimental autoimmune encephalomyelitis (EAE). Axonal repair was measured by upregulation of GAP43. Enzyme-linked immunosorbent assay, flow cytometry, and 3H-thymidine incorporation were used to determine immunological changes in myelin-specific T cells in mice with EAE.
The siRNA-NogoA suppressed Nogo-A expression in vitro and in vivo. Systemic administration of siRNA-NogoA ameliorated EAE and promoted axonal repair, as demonstrated by enhanced GAP43+ axons in the lesions. Myelin-specific T-cell proliferation and cytokine production were unchanged in the siRNA-NogoA–treated mice.
Silencing Nogo-A in EAE promotes functional recovery. The therapeutic benefit appears to be mediated by axonal growth and repair, and is not attributable to changes in the encephalitogenic capacity of the myelin-specific T cells. Silencing Nogo-A may be a therapeutic option for MS patients to prevent permanent functional deficits caused by immune-mediated axonal damage. ANN NEUROL 2010;67:498–507