机构：[1]Department of Medicine (RMH), University of Melbourne, Australia[2]The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia[3]Department of Radiology, Xuanwu Hospital, Capital Medical University, China放射科[4]Centre for Neuroscience Research, University of Melbourne, Australia[5]Department of Anatomy and Neuroscience, University of Melbourne, Australia[6]CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, China[7]Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, China[8]Department of Ophthalmology, University of Hong Kong, China[9]Department of Discovery Neurobiology, Biogen, USA
Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated.
In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves.
The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models.
In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration.
These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.
基金：
This work was supported by Biogen (Cambridge,
MA, USA), which also funded writing and editorial
support. Melissa M Gresle is the recipient of a
Multiple Sclerosis Research Australia Fellowship.
Helmut Butzkueven is the recipient of a National
Health and Medical Research Council (NHMRC)
Practitioner Fellowship (1080518), NHMRC Project Grants (1065157, 1083539), and an NHMRC
Centre of Excellence Award (1001216).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
无
最新[2025]版：
大类|4 区医学
小类|4 区临床神经病学
第一作者：
第一作者机构：[1]Department of Medicine (RMH), University of Melbourne, Australia[2]The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia
通讯作者：
通讯机构：[*1]Department of Discovery Neurobiology[*1]Department of Discovery Neurobiology
推荐引用方式(GB/T 7714)：
Melissa M Gresle,Yaou Liu,Trevor J Kilpatrick,et al.Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve.[J].Multiple sclerosis journal - experimental, translational and clinical.2016,2:1-13.doi:10.1177/2055217316641704.
APA：
Melissa M Gresle,Yaou Liu,Trevor J Kilpatrick,Dennis Kemper,Qi-Zhu Wu...&Sha Mi.(2016).Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve..Multiple sclerosis journal - experimental, translational and clinical,2,
MLA：
Melissa M Gresle,et al."Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve.".Multiple sclerosis journal - experimental, translational and clinical 2.(2016):1-13
