Anti‐Nogo on the go: from animal models to a clinical trial
Anti‐Nogo on the go: from animal models to a clinical trial
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DOI：
10.1111/j.1749-6632.2010.05566.x
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发表时间：
2010-06
影响因子：
5.2
通讯作者：
B. Zörner;M. Schwab
中科院分区：
文献类型：
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作者：
B. Zörner;M. Schwab
成人中枢神经系统（CNS）的小病变通常有良好的预后，部分基于自发神经鞘发芽和投射重排的广泛功能恢复。这在皮层中有很好的记录，但这些变化也可能发生在脊髓中。Nogo‐A是存在于中枢神经系统髓鞘中的一种抑制神经突生长的蛋白质。大鼠和猕猴的脊髓损伤（SCI）模型表明，用Nogo - A的功能阻断抗体治疗可导致生长特异性蛋白上调，增强纤维的再生和代偿发芽，并在脊髓中形成新的功能连接。在单侧感觉运动皮层病变的动物中，经过Nogo‐A抗体治疗后，来自完整皮质系统的纤维穿过中线，向无神经支配的脑干或脊髓提供神经支配。行为测试显示，使用Nogo - A抗体治疗脊髓或脑损伤动物的功能恢复有显著改善。一项应用抗Nogo - A抗体治疗急性SCI患者的I期临床试验已经成功进行，一项多中心、多国的II期试验目前正在准备中。
Small lesions of the adult central nervous system (CNS) often have a good prognosis with extensive functional recovery based in part on spontaneous neuritic sprouting and rearrangements of projections. This is well documented for the cortex, but these changes can also occur in the spinal cord. Nogo‐A is a protein present in CNS myelin that inhibits neurite growth. Models of spinal cord injury (SCI) in rats and macaque monkeys demonstrate that treatment with function‐blocking antibodies of Nogo‐A results in an upregulation of growth‐specific proteins, enhanced regenerative and compensatory sprouting of fibers, and the formation of new functional connections in the spinal cord. In animals with unilateral sensorimotor cortex lesions followed by Nogo‐A antibody treatment, fibers from the intact corticofugal system crossed the midline, supplying innervation to the denervated brain stem or spinal cord. Behavioral tests showed marked improvements of functional recovery in the Nogo‐A antibody treated spinal cord‐ or brain‐injured animals. A Phase I clinical trial applying anti‐Nogo‐A antibody to subjects with acute SCI has been successfully conducted and a multicentric, multinational Phase II trial is currently in preparation.