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    Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve.

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    Author
    Gresle, MM; Liu, Y; Kilpatrick, TJ; Kemper, D; Wu, Q-Z; Hu, B; Fu, Q-L; So, K-F; Sheng, G; Huang, G; ...
    Date
    2016-01
    Source Title
    Multiple Sclerosis Journal - Experimental, Translational and Clinical
    Publisher
    SAGE Publications
    University of Melbourne Author/s
    Gresle, Melissa; Butzkueven, Helmut; Kilpatrick, Trevor; KEMPER, DENNIS
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Medicine and Radiology
    Centre for Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Gresle, M. M., Liu, Y., Kilpatrick, T. J., Kemper, D., Wu, Q. -Z., Hu, B., Fu, Q. -L., So, K. -F., Sheng, G., Huang, G., Pepinsky, B., Butzkueven, H. & Mi, S. (2016). Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve.. Mult Scler J Exp Transl Clin, 2, pp.2055217316641704-. https://doi.org/10.1177/2055217316641704.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260368
    DOI
    10.1177/2055217316641704
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433342
    Abstract
    BACKGROUND: Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated. OBJECTIVE: In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves. METHODS: The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models. RESULTS: In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration. CONCLUSION: These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.

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