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LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis

Nature Medicine volume 13, pages 12281233 (2007) | Download Citation

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Abstract

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.

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Author information

Author notes

    • Sha Mi
    • , Bing Hu
    •  & Wutian Wu

    These authors contributed equally to this manuscript.

    • Bing Hu

    Present address: School of Life Science, The University of Science and Technology of China, Hefei, Anhui 230027, China.

Affiliations

  1. Biogen Idec Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA.

    • Sha Mi
    • , Kyungmin Hahm
    • , Yi Luo
    • , Blake Pepinsky
    • , Zhaohui Shao
    • , Christilyn Graff
    • , Ellen Garber
    •  & Vincent Jung
  2. Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

    • Bing Hu
    • , Qiuju Yuan
    • , Wai Man Wong
    • , Li Wang
    • , Huanxing Su
    • , Tak-Ho Chu
    • , Jiasong Guo
    • , Wenming Zhang
    • , Kwok-Fai So
    •  & Wutian Wu
  3. State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

    • Kwok-Fai So
    •  & Wutian Wu
  4. Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

    • Kwok-Fai So
  5. Research Center of Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

    • Wutian Wu
  6. Department of Electrical and Electronic Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

    • Edward Sai Kam Hui
    •  & Ed Xuekui Wu

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DOI

https://doi.org/10.1038/nm1664

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