Nature Medicine：吴武田小组治疗脱髓鞘疾病新方法
来自美生物制药公司Biogen Idec Inc、中国香港大学解剖学系和脑与认知科学国家重点实验室（State Key Laboratory of Brain and Cognitive Sciences）等单位的研究人员发现了一种治疗中枢神经系统CNS脱髓鞘疾病（demyelinating diseases）的新方法。这一研究成果公布在《自然—医学》杂志上。
领导这一研究的是香港大学医学院解剖学系副教授，中山大学客座教授的吴武田教授，其一直致力于神经损伤和再生机制方面的基础研究。
脱髓鞘疾病（demyelinating diseases），譬如多发性硬化症（multiple sclerosis，MS，一种自体免疫性疾病(autoimmune disease)，即患者体内的免疫系统无法分辨何者是自己的细胞，何者为外来侵犯物，造成免疫系统攻击自身的组织）的一个重要特征就是神经细胞周围髓鞘（myelin sheath）丢失，这主要是因为中枢神经系统（central nervous system，CNS）中发生了炎症反应和胶质增生（gliosis）。
因此目前的治疗主要是靶向抗炎机制，达到阻碍或延缓疾病扩散的目的，而针对轴突髓鞘质（myelin）的一种方法则提供了抑制以及可能逆转疾病扩散的新治疗方法，之前的研究发现，含亮氨酸重复序列和免疫球蛋白结构域的Nogo受体作用蛋白（LINGO-1）是一种体内体外少突胶质细胞（Oligodendrocyte）分化和髓鞘（myelination）的负调控因子。
在这篇文章中，研究人员利用LINGO-1基因敲除或者抗LINGO-1功能的抗体造成LINGO-1功能缺失，结果发现这种缺陷型中实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis）功能复原，这通过生物性轴突完整性增加——弥散张量磁共振成像（magnetic resonance diffusion tensor imaging）和髓鞘新形成——电子显微（electron microscopy）获得确认。从而研究人员提出针对LINGO-1或其途径的对抗治疗是一种治疗中枢神经系统CNS脱髓鞘疾病的新方法。
原始出处:
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
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.
- 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.
Correspondence to: Wutian Wu2,3,5,7 e-mail: wtwu@hkucc.hku.hk
Correspondence to: Sha Mi1,7 e-mail: sha.mi@biogenidec.com
相关报道:
急性播散性脑脊髓炎 acute disseminated encephalomyelitis
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