title: Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis.
abstract: 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.
authors: Elena
authors: E
authors: Demicheva
authors: Yi-Fang
authors: YF
authors: Cui
authors: Philip
authors: P
authors: Bardwell
authors: Stefan
authors: S
authors: Barghorn
authors: Martina
authors: M
authors: Kron
authors: Axel H
authors: AH
authors: Meyer
authors: Martin
authors: M
authors: Schmidt
authors: Björn
authors: B
authors: Gerlach
authors: Mary
authors: M
authors: Leddy
authors: Eve
authors: E
authors: Barlow
authors: Elizabeth
authors: E
authors: O'Connor
authors: Chee-Ho
authors: CH
authors: Choi
authors: Lili
authors: L
authors: Huang
authors: Geertruida M
authors: GM
authors: Veldman
authors: Horea
authors: H
authors: Rus
authors: Alireza P
authors: AP
authors: Shabanzadeh
authors: Nardos G
authors: NG
authors: Tassew
authors: Philippe P
authors: PP
authors: Monnier
authors: Thomas
authors: T
authors: Müller
authors: Peter A
authors: PA
authors: Calabresi
authors: Hans
authors: H
authors: Schoemaker
authors: Bernhard K
authors: BK
authors: Mueller
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C502259:RGM protein, rat