针对神经肌肉接头的靶向治疗：概念验证。
Targeting therapy to the neuromuscular junction: proof of concept.
机构信息
Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
出版信息
Muscle Nerve. 2014 May;49(5):749-56. doi: 10.1002/mus.24057.
INTRODUCTION
The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ.
METHODS
A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG.
RESULTS
Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally acquired MG treated with scFV-35-DAF showed less weakness and a reduction of complement deposition.
CONCLUSIONS
We demonstrate a method to effectively target a therapeutic agent to the NMJ.
简介
重症肌无力 (MG) 的病理学部位是神经肌肉接头 (NMJ)。我们的目标是确定将补体抑制作用靶向 NMJ 的能力。
方法
合成了一种针对乙酰胆碱受体α亚单位的单链抗体（scFv-35），并将其与衰变加速因子 (DAF) 偶联（scFv-35-DAF）。在实验性获得性 MG 的被动模型中测试了 scFv-35-DAF。
结果
尽管确认其定位于 NMJ 且没有补体激活相关的组织破坏证据，但 scFv-35-DAF 给药至缺乏内在补体抑制剂的小鼠并未引起肌无力。用 scFV-35-DAF 治疗实验性获得性 MG 的大鼠表现出较弱的肌无力和补体沉积减少。
结论
我们证明了一种将治疗剂有效靶向 NMJ 的方法。
Zotero 插件