Department of Neurology, University of Rostock, Rostock, Germany.
BioDrugs. 2012 Apr 1;26(2):e1-9. doi: 10.2165/11599840-000000000-00000.
Botulinum toxin type A is a 150 kD protein produced by Clostridium botulinum, which exists in a complex with up to six additional proteins. The ability of botulinum toxin to inhibit acetylcholine release at the neuromuscular junction has been exploited for use in medical conditions characterized by muscle hyperactivity. As such, botulinum toxin is widely recommended by international treatment guidelines for movement disorders and it has a plethora of other clinical and cosmetic indications. The chronic nature of these conditions requires repeated injections of botulinum toxin, usually every few months. Multiple injections can lead to secondary treatment failure in some patients that may be associated with the production of neutralizing antibodies directed specifically against the neurotoxin. However, the presence of such antibodies does not always render patients non-responsive. The reported prevalence of immunoresistance varies greatly, depending on factors such as study design and treated indication. This review presents what is currently known about the immunogenicity of botulinum toxin and how this impacts upon patient non-response to treatment. The complexing proteins may act as adjuvants and stimulate the immune response. Their role and that of neutralizing and non-neutralizing antibodies in the response to botulinum toxin is discussed, together with an assessment of current neutralizing antibody measurement techniques. Botulinum toxin preparations with different compositions and excipients have been developed. The major commercially available preparations of botulinum toxin are Botox (onabotulinumtoxin A; Allergan, Inc., Ireland), Dysport (abobotulinumtoxin A; Ipsen Ltd, UK), and Xeomin (incobotulinumtoxin A; botulinum toxin type A [150 kD], free from complexing proteins; NT 201; Merz Pharmaceuticals GmbH, Germany). The new preparations of botulinum toxin aim to minimize the risk of immunoresistance in patients being treated for chronic clinical conditions.
A型肉毒毒素是由肉毒梭菌产生的一种 150kD 蛋白，它与多达六种额外的蛋白质形成复合物。肉毒毒素抑制运动终板乙酰胆碱释放的能力已被用于治疗肌肉过度活跃的疾病。因此，肉毒毒素被国际治疗指南广泛推荐用于运动障碍，它还有许多其他的临床和美容适应症。这些疾病的慢性性质需要反复注射肉毒毒素，通常每几个月一次。在一些患者中，多次注射可能导致继发性治疗失败，这可能与针对神经毒素的中和抗体的产生有关。然而，并非所有患者都会因此产生无反应。免疫抵抗的报告发生率差异很大，取决于研究设计和治疗适应症等因素。本综述介绍了目前已知的肉毒毒素的免疫原性以及这如何影响患者对治疗的无反应。复合蛋白可能作为佐剂刺激免疫反应。本文讨论了它们在肉毒毒素反应中的作用以及中和和非中和抗体的作用，并评估了当前中和抗体测量技术。已经开发了具有不同成分和赋形剂的肉毒毒素制剂。主要的市售肉毒毒素制剂有 Botox（onabotulinumtoxin A；Allergan，Inc.，Ireland）、Dysport（abobotulinumtoxin A；Ipsen Ltd.，UK）和 Xeomin（incobotulinumtoxin A；肉毒毒素 A 型[150kD]，不含复合蛋白；NT 201；Merz Pharmaceuticals GmbH，Germany）。这些新的肉毒毒素制剂旨在降低治疗慢性临床疾病的患者发生免疫抵抗的风险。
