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首页> 外文期刊>Neurotherapeutics >Targeting Therapeutic Antibodies to the CNS: a Comparative Study of Intrathecal, Intravenous, and Subcutaneous Anti-Nogo A Antibody Treatment after Stroke in Rats
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Targeting Therapeutic Antibodies to the CNS: a Comparative Study of Intrathecal, Intravenous, and Subcutaneous Anti-Nogo A Antibody Treatment after Stroke in Rats

机译：针对CNS的治疗抗体：大鼠中风后鞘内，静脉内，皮下抗Nogo A抗体治疗的对比研究

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Antibody-based therapeutics targeting CNS antigens emerge as promising treatments in neurology. However, access to the CNS is limited by the blood–brain barrier. We examined the effects of a neurite growth-enhancing anti-Nogo A antibody therapy following 3 routes of administration—intrathecal (i.t.), intravenous (i.v.), and subcutaneous (s.c.)—after large photothrombotic strokes in adult rats. Intrathecal treatment of full-length IgG anti-Nogo A antibodies enhanced recovery of the grasping function, but intravenous or subcutaneous administration had no detectable effect in spite of large amounts of antibodies in the peripheral circulation. Thus, in contrast to intravenous and subcutaneous delivery, intrathecal administration is an effective and reliable way to target CNS antigens. Our data reveal that antibody delivery to the CNS is far from trivial. While intrathecal application is feasible and guarantees defined antibody doses in the effective range for a biological function, the identification and establishment of easier routes of administration remains an important task to facilitate antibody-based future therapies of CNS disorders. Electronic supplementary material The online version of this article (10.1007/s13311-020-00864-z) contains supplementary material, which is available to authorized users.
机译：靶向CNS抗原的基于抗体的治疗剂作为神经内科的有前途治疗结果。但是，对CNS的访问受到血脑屏障的限制。我们检查了神经突生长增强抗Nogo A抗体治疗的影响，抗体治疗3次施用鞘内（I.T.），静脉注射（I.V.）和皮下（S.） - 在成年大鼠中大的刻癌术后。全长IgG抗Nogo抗体治疗A抗体增强了抓握功能的恢复，但静脉内或皮下给药在外围循环中仍然没有可检测的效果。因此，与静脉内和皮下递送形成鲜明对比，鞘内给药是靶向CNS抗原的有效且可靠的方法。我们的数据揭示了对CNS的抗体传递远非微不足道。虽然鞘内应用是可行的，并且保证在生物学功能的有效范围内定义的抗体剂量，但识别和建立更容易的给药途径仍然是促进基于抗体的CNS障碍治疗的重要任务。电子补充材料本文的在线版本（10.1007 / s13311-020-00864-z）包含补充材料，可供授权用户使用。

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