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.

中文翻译：

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针对中枢神经系统的靶向治疗性抗体：大鼠中风后鞘内、静脉和皮下抗 Nogo A 抗体治疗的比较研究。

靶向中枢神经系统抗原的基于抗体的疗法在神经病学中成为有前景的疗法。然而，进入中枢神经系统受到血脑屏障的限制。我们在成年大鼠的大光血栓形成中风后，通过鞘内 (it)、静脉内 (iv) 和皮下 (sc) 3 种给药途径检查了神经突生长促进抗 Nogo A 抗体疗法的效果。全长 IgG 抗 Nogo A 抗体鞘内治疗增强了抓握功能的恢复，但静脉或皮下给药尽管外周循环中有大量抗体，但没有可检测到的效果。因此，与静脉内和皮下给药相比，鞘内给药是靶向 CNS 抗原的有效且可靠的方法。我们的数据表明，将抗体递送至 CNS 绝非易事。虽然鞘内应用是可行的，并保证在生物功能的有效范围内确定抗体剂量，但识别和建立更简单的给药途径仍然是促进基于抗体的 CNS 疾病未来治疗的重要任务。