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

TitleBlocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve
Authors
Issue Date2016
PublisherSage Publications Ltd. The Journal's web site is located at http://msj.sagepub.com/
Citation
Multiple Sclerosis Journal, 2016, v. 2, p. article no. 2055217316641704 How to Cite?
AbstractBackground 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.
Persistent Identifierhttp://hdl.handle.net/10722/230566
ISSN
2015 Impact Factor: 4.671
2015 SCImago Journal Rankings: 2.177

 

DC FieldValueLanguage
dc.contributor.authorGresle, M. M.-
dc.contributor.authorLiu, Y-
dc.contributor.authorKilpatrick, T. J.-
dc.contributor.authorKemper, D-
dc.contributor.authorWu, QZ-
dc.contributor.authorHu, B-
dc.contributor.authorFu, QL-
dc.contributor.authorSo, KF-
dc.contributor.authorSheng, G-
dc.contributor.authorHuang, G-
dc.contributor.authorPepinsky, B-
dc.contributor.authorButzkueven, H-
dc.contributor.authorMi, S-
dc.date.accessioned2016-08-23T14:17:47Z-
dc.date.available2016-08-23T14:17:47Z-
dc.date.issued2016-
dc.identifier.citationMultiple Sclerosis Journal, 2016, v. 2, p. article no. 2055217316641704-
dc.identifier.issn1352-4585-
dc.identifier.urihttp://hdl.handle.net/10722/230566-
dc.description.abstractBackground 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.-
dc.languageeng-
dc.publisherSage Publications Ltd. The Journal's web site is located at http://msj.sagepub.com/-
dc.relation.ispartofMultiple Sclerosis Journal-
dc.rightsMultiple Sclerosis Journal. Copyright © Sage Publications Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleBlocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve-
dc.typeArticle-
dc.identifier.emailSo, KF: hrmaskf@hku.hk-
dc.identifier.authoritySo, KF=rp00329-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1177/2055217316641704-
dc.identifier.hkuros261408-
dc.identifier.volume2-
dc.identifier.spagearticle no. 2055217316641704-
dc.identifier.epagearticle no. 2055217316641704-
dc.publisher.placeUnited Kingdom-

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