Brain Research Institute, University of Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland.
Central Institute of Mental Health, University of Heidelberg, J5, 68159, Mannheim, Germany.
Neurotherapeutics. 2020 Jul;17(3):1153-1159. doi: 10.1007/s13311-020-00864-z.
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.
针对中枢神经系统抗原的抗体治疗在神经病学中具有广阔的应用前景。然而，血脑屏障限制了药物进入中枢神经系统的能力。我们在成年大鼠的大型光血栓性中风后，通过鞘内（i.t.）、静脉内（i.v.）和皮下（s.c.）三种给药途径，研究了神经营养生长增强型抗 Nogo A 抗体治疗的效果。鞘内给予全长 IgG 抗 Nogo A 抗体可增强抓握功能的恢复，但静脉内或皮下给予即使在外周循环中有大量抗体也没有可检测到的效果。因此，与静脉内和皮下给药相比，鞘内给药是一种靶向中枢神经系统抗原的有效且可靠的方法。我们的数据表明，抗体向中枢神经系统的输送远非易事。虽然鞘内应用是可行的，并能保证有效范围内的特定抗体剂量，以发挥生物功能，但鉴定和建立更简单的给药途径仍然是一项重要任务，以促进基于抗体的中枢神经系统疾病的未来治疗。
