Ipsen Bioinnovation, Abingdon OX14 4RY, UK.
Ipsen Pharma, Cambridge, MA 02142, USA.
Toxins (Basel). 2018 Dec 13;10(12):535. doi: 10.3390/toxins10120535.
Botulinum neurotoxin type-A (BoNT-A) blocks the release of acetylcholine from peripheral cholinergic nerve terminals and is an important option for the treatment of disorders characterised by excessive cholinergic neuronal activity. Several BoNT-A products are currently marketed, each with unique manufacturing processes, excipients, formulation, and non-interchangeable potency units. Nevertheless, the effects of all the products are mediated by the 150 kDa BoNT-A neurotoxin. We assessed the quantity and light chain (LC) activity of BoNT-A in three commercial BoNT-A products (Dysport; Botox; Xeomin). We quantified 150 kDa BoNT-A by sandwich ELISA and assessed LC activity by EndoPep assay. In both assays, we assessed the results for the commercial products against recombinant 150 kDa BoNT-A. The mean 150 kDa BoNT-A content per vial measured by ELISA was 2.69 ng/500 U vial Dysport, 0.90 ng/100 U vial Botox, and 0.40 ng/100 U vial Xeomin. To present clinically relevant results, we calculated the 150 kDa BoNT-A/US Food and Drug Administration (FDA)-approved dose in adult upper limb spasticity: 5.38 ng Dysport (1000 U; 2 × 500 U vials), 3.60 ng Botox (400 U; 4 × 100 U vials), and 1.61 ng Xeomin (400 U; 4 × 100 U vials). EndoPep assay showed similar LC activity among BoNT-A products. Thus, greater amounts of active neurotoxin are injected with Dysport, at FDA-approved doses, than with other products. This fact might explain the long duration of action reported across multiple indications, which benefits patients, caregivers, clinicians, and healthcare systems.
A型肉毒毒素（BoNT-A）可阻断周围胆碱能神经末梢乙酰胆碱的释放，是治疗过度胆碱能神经元活动引起的疾病的重要选择。目前有几种 BoNT-A 产品上市，每种产品都有独特的生产工艺、赋形剂、配方和不可互换的效价单位。然而，所有产品的作用都是通过 150 kDa BoNT-A 神经毒素介导的。我们评估了三种商业 BoNT-A 产品（Dysport、Botox 和 Xeomin）中 BoNT-A 的数量和轻链（LC）活性。我们通过夹心 ELISA 定量测定 150 kDa BoNT-A，并通过 EndoPep 测定法评估 LC 活性。在这两种测定中，我们将商业产品的结果与重组 150 kDa BoNT-A 进行了比较。通过 ELISA 测量，每个 500 U 西林瓶的 Dysport 中 150 kDa BoNT-A 的平均含量为 2.69ng，每个 100 U 西林瓶的 Botox 为 0.90ng，每个 100 U 西林瓶的 Xeomin 为 0.40ng。为了呈现临床相关的结果，我们计算了成人上肢痉挛性疾病中经美国食品和药物管理局（FDA）批准的剂量的 150 kDa BoNT-A：5.38ng Dysport（1000U；2×500U 西林瓶）、3.60ng Botox（400U；4×100U 西林瓶）和 1.61ng Xeomin（400U；4×100U 西林瓶）。EndoPep 测定法显示 BoNT-A 产品之间的 LC 活性相似。因此，与其他产品相比，以 FDA 批准的剂量注射 Dysport 时，会注入更多的有效神经毒素。这一事实可能解释了在多种适应症中报告的较长作用持续时间，这使患者、护理人员、临床医生和医疗保健系统受益。
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