Botulinum neurotoxin serotype D is poorly effective in humans: An in vivo electrophysiological study
Botulinum neurotoxin serotype D is poorly effective in humans: An in vivo electrophysiological study
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DOI：
10.1016/j.clinph.2012.11.004
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发表时间：
2013-05-01
影响因子：
4.7
通讯作者：
Rossetto, Ornella
中科院分区：
文献类型：
--
作者：
Eleopra, Roberto;Montecucco, Cesare;Rossetto, Ornella
目的：肉毒神经毒素作用于神经末梢，阻断神经递质的释放。它们的效力是由于它们的酶活性和与神经元的高亲和力结合。A型肉毒杆菌毒素用于治疗以外周胆碱能神经末梢过度活跃为特征的人类疾病，但有些患者对A型肉毒杆菌毒素具有耐药性或产生耐药性。这可以通过使用其他肉毒杆菌毒素来克服，并且已经用不同的毒素血清型进行了研究。肉毒杆菌神经毒素D型从来没有在人体内进行过测试，因此，我们研究了这种毒素在小鼠和人类muscle.Methods的行动：肉毒杆菌毒素D型效力测定小鼠hemidiaphragm和大鼠神经元培养。根据这些实验，决定了在人类志愿者中注射的剂量。结果：D型肉毒毒素对人体骨骼肌麻痹作用不明显。结论：D型肉毒毒素对小鼠的作用很强，对人体几乎无效。这些结果为D型毒素与神经元表面受体结合的机制提供了新的线索。(C)2012年国际临床神经生理学联合会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Objective: Botulinum neurotoxins act on nerve endings and block neurotransmitter release. Their potency is due to their enzymatic activity and high affinity binding to neurons. Botulinum toxin type A is used in the treatment of human diseases characterized by hyperactivity of peripheral cholinergic nerve terminals, but some patients are or become resistant to it. This can be overcome by using other botulinum toxins, and studies have been performed with different toxin serotypes. Botulinum neurotoxin type D has never been tested in humans in vivo, and, therefore, we investigated the action of this toxin in mouse and human muscles.Methods: Botulinum toxin type D potency was determined on mouse hemidiaphragm and on rat neuronal cultures. From these experiments, doses to be injected in human volunteers were decided. The compound muscle action potential of toxin-injected Extensor Digitorum Brevis muscle was measured at different times points after injection in human volunteers.Results: Botulinum toxin type D is poorly effective in inducing human skeletal muscle paralysis.Conclusions: Botulinum toxin type D is very potent in mice and almost ineffective in humans in vivo.Significance: The results shed new light on the mechanism of toxin type D binding to the neuronal surface receptors. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.