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01-09-2017 | Original Paper

Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology

Authors: Benjamin V. Ineichen, Sandra Kapitza, Christiane Bleul, Nicolas Good, Patricia S. Plattner, Maryam S. Seyedsadr, Julia Kaiser, Marc P. Schneider, Björn Zörner, Roland Martin, Michael Linnebank, Martin E. Schwab

Published in: Acta Neuropathologica | Issue 3/2017

Abstract

Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution.

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Title: Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology
Authors: Benjamin V. Ineichen
Sandra Kapitza
Christiane Bleul
Nicolas Good
Patricia S. Plattner
Maryam S. Seyedsadr
Julia Kaiser
Marc P. Schneider
Björn Zörner
Roland Martin
Michael Linnebank
Martin E. Schwab
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 3/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1745-3

Keynote webinar | Spotlight on sleep in brain health

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Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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