Nature Medicine 13, 1228 - 1233 (2007)
Published online: 30 September 2007 | doi:10.1038/nm1664
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis
Sha Mi1,7, Bing Hu2,7,8, Kyungmin Hahm1, Yi Luo1, Edward Sai Kam Hui6, Qiuju Yuan2, Wai Man Wong2, Li Wang2, Huanxing Su2, Tak-Ho Chu2, Jiasong Guo2, Wenming Zhang2, Kwok-Fai So2,3,4, Blake Pepinsky1, Zhaohui Shao1, Christilyn Graff1, Ellen Garber1, Vincent Jung1, Ed Xuekui Wu6 & Wutian Wu2,3,5,7
AbstractDemyelinating 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.Top of page
- Biogen Idec Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA.
- Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
- Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
- Research Center of Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
- Department of Electrical and Electronic Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
- These authors contributed equally to this manuscript.
- Present address: School of Life Science, The University of Science and Technology of China, Hefei, Anhui 230027, China.