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Blocking Nogo Receptor 1 Promotes Functional Regeneration after Spinal Cord Injury | OMICS International | Abstract
ISSN: 2329-6895

Journal of Neurological Disorders
Open Access

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Research Article

Blocking Nogo Receptor 1 Promotes Functional Regeneration after Spinal Cord Injury

Mezler M1*, Moeller A1, Mueller BK1, Meyer AH1, Schmidt MK1, Ghayur T2, Barlow E2, Labkovsky B2, Devanarayan V3, Norreel JC4 and Mueller R1
1Neuroscience Research, Global Pharmaceutical Research & Development, AbbVie, 67061 Ludwigshafen, Germany
2AbbVie Bioresearch Center, 100 Research Drive, Worcester MA 01605, USA
3Exploratory Statistics, AbbVie, Souderton, PA 18964, USA
4Pharmaxon, IBDM, Parc Scientifique de Luminy, Case 907, 13288 Marseille Cedex 09, France; current address : KIS Healthcare Ltd. PMI Plc., Church Road, Bookham, Surrey KT23 3EU, UK
Corresponding Author : Mario Mezler
AbbVie Deutschland GmbH & Co. KG
Neuroscience Discovery
Department of Biology
Knollstrasse 50
67061 Ludwigshafen, Germany
Tel: (49) 621 589 4602
Fax: (49) 621 589 3232
E-mail: [email protected]
Received June 18, 2013; Accepted August 12, 2013; Published August 15, 2013
Citation: Mezler M, Moeller A, Mueller BK, Meyer AH, Schmidt MK, et al. (2013) Blocking Nogo Receptor 1 Promotes Functional Regeneration after Spinal Cord Injury. J Neurol Disord 1:128. doi: 10.4172/2329-6895.1000128
Copyright: © 2013 Mezler M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

An insult to the mammalian spinal cord often results in persistent functional deficits. Proteins in CNS myelin are important determinants of this situation as they inhibit neurite growth. Among those proteins Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and myelin-associated glycoprotein (MAG) all bind to the neuronal Nogo-66 receptor (NgR1) and thereby block neuronal regeneration after injury. Neutralizing the interaction between the inhibitory ligands and NgR1 may alleviate the inhibition and therefore result in increased recovery after injury. Thus, antibodies neutralizing ligand/receptor interaction might have therapeutic value.

From a set of 300 monoclonal anti-NgR1 antibodies one anti-NgR1 ligand blocking antibody (mAb50) was selected for in vivo studies. mAb50 binds with high affinity (below 100 pM) to human and rat NgR1, competes for binding of a ligand peptide (derived from Nogo-A: Nogo66) to the isolated NgR1 protein and cellular NgR1, and reduces the inhibitory effects of Nogo66 on neurite outgrowth in differentiated human NTera2 cells and rat dorsal root ganglion neurons. In a rat spinal cord hemisection model mAb50 enhanced functional locomotor recovery. These data suggest that neutralization of NgR1 activity with an antibody may be a valuable strategy to neutralize neurite outgrowth inhibition in the mammalian CNS. Thus anti-NgR1 antibodies are a potential approach for the treatment of spinal cord injury and even neurodegenerative diseases.

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