Targeting Repulsive Guidance Molecule A to Promote Regeneration and Neuroprotection in Multiple Sclerosis

被引：62

作者：

Demicheva, Elena ^{[1
]}

Cui, Yi-Fang ^{[1
]}

Bardwell, Philip ^{[2
]}

Barghorn, Stefan ^{[1
]}

Kron, Martina ^{[1
]}

Meyer, Axel H. ^{[1
]}

Schmidt, Martin ^{[1
]}

Gerlach, Bjoern ^{[1
]}

Leddy, Mary ^{[2
]}

Barlow, Eve ^{[2
]}

O'Connor, Elizabeth ^{[2
]}

Choi, Chee-Ho ^{[2
]}

Huang, Lili ^{[2
]}

Veldman, Geertruida M. ^{[2
]}

Rus, Horea ^{[3
]}

Shabanzadeh, Alireza P. ^{[4
]}

Tassew, Nardos G. ^{[4
]}

Monnier, Philippe P. ^{[4
]}

Mueller, Thomas ^{[5
]}

Calabresi, Peter A. ^{[6
]}

Schoemaker, Hans ^{[1
]}

Mueller, Bernhard K. ^{[1
]}

机构：

[1] AbbVie Deutschland GmbH & Co KG, Neurosci Res Res & Dev, D-67061 Ludwigshafen, Germany

[2] AbbVie Biores Ctr, Worcester, MA 01605 USA

[3] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA

[4] Toronto Western Res Inst, Genet & Dev Div, Toronto, ON M5T 2S8, Canada

[5] St Joseph Hosp, Dept Neurol, D-13088 Berlin, Germany

[6] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA

来源：

CELL REPORTS | 2015年 / 10卷 / 11期

关键词：

OPTICAL COHERENCE TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM; RETINAL GANGLION-CELLS; SPINAL-CORD-INJURY; AXONAL GROWTH; AUTOIMMUNE ENCEPHALOMYELITIS; RGMA INHIBITION; VISUAL-SYSTEM; ANIMAL-MODEL; EXPRESSION;

D O I：

10.1016/j.celrep.2015.02.048

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Repulsive guidance molecule A (RGMa) is a potent inhibitor of neuronal regeneration and a regulator of cell death, and it plays a role in multiple sclerosis (MS). In autopsy material from progressive MS patients, RGMa was found in active and chronic lesions, as well as in normal-appearing gray and white matter, and was expressed by cellular meningeal infiltrates. Levels of soluble RGMa in the cerebrospinal fluid were decreased in progressive MS patients successfully treated with intrathecal corticosteroid triamcinolone acetonide (TCA), showing functional improvements. In vitro, RGMa monoclonal antibodies (mAbs) reversed RGMa-mediated neurite outgrowth inhibition and chemorepulsion. In animal models of CNS damage and MS, RGMa antibody stimulated regeneration and remyelination of damaged nerve fibers, accelerated functional recovery, and protected the retinal nerve fiber layer as measured by clinically relevant optic coherence tomography. These data suggest that targeting RGMa is a promising strategy to improve functional recovery in MS patients.

引用

页码：1887 / 1898

页数：12

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