LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Demyelinating diseases, such as multiple sclerosis, are characterized by the loss of the myelin sheath around neurons, owing to inflammation and gliosis in the central nervous system (CNS). Current treatments therefore target anti-inflammatory mechanisms to impede or slow disease progression. The identification of a means to enhance axon myelination would present new therapeutic approaches to inhibit and possibly reverse disease progression. Previously, LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) has been identified as an in vitro and in vivo negative regulator of oligodendrocyte differentiation and myelination. Here we show that loss of LINGO-1 function by Lingo1 gene knockout or by treatment with an antibody antagonist of LINGO-1 function leads to functional recovery from experimental autoimmune encephalomyelitis. This is reflected biologically by improved axonal integrity, as confirmed by magnetic resonance diffusion tensor imaging, and by newly formed myelin sheaths, as determined by electron microscopy. Antagonism of LINGO-1 or its pathway is therefore a promising approach for the treatment of demyelinating diseases of the CNS.
Mi
Sha
S
Biogen Idec Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. sha.mi@biogenidec.com
Hu
Bing
B
Hahm
Kyungmin
K
Luo
Yi
Y
Kam Hui
Edward Sai
ES
Yuan
Qiuju
Q
Wong
Wai Man
WM
Wang
Li
L
Su
Huanxing
H
Chu
Tak-Ho
TH
Guo
Jiasong
J
Zhang
Wenming
W
So
Kwok-Fai
KF
Pepinsky
Blake
B
Shao
Zhaohui
Z
Graff
Christilyn
C
Garber
Ellen
E
Jung
Vincent
V
Wu
Ed Xuekui
EX
Wu
Wutian
W
D000818:Animals; D001369:Axons / Q000000981:diagnostic imaging / Q000502:physiology* / Q000648:ultrastructure; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000473:pathology; D007278:Injections, Spinal; D008565:Membrane Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014057:Tomography, X-Ray Computed
C523678:LINGO1 protein, mouse; C525164:LINGO1 protein, rat; D008565:Membrane Proteins; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins