Abstract
Botulinum toxin (BT) consists of botulinum neurotoxin and complexing proteins (CPs). CPs might provide mechanical protection for botulinum neurotoxin. As incobotulinumtoxinA (INCO, Xeomin®) does not contain CPs, we wanted to compare its mechanical stability to that of onabotulinumtoxinA (ONA, Botox®) containing CPs. For this, ONA and INCO were reconstituted without mechanical stress (NS) and with mechanical stress (WS) generated by a recently introduced stress test. Potencies were then measured by the paralysis times (PTs) in the mouse diaphragm assay. ONA-PT was 75.8 ± 10.3 min (n = 6) under NS and 116.7 ± 29.8 min (n = 6) under WS (two-tailed t test, p = 0.002). Mechanical stress increased the ONA-PT by 35.0% on the Growth Percentage Index. INCO-PT was 66.0 ± 7.0 min for NS and 76.0 ± 1.0 min for WS (t test, p = 0.129). Mechanical stress increased the INCO-PT by 13.2% on the Growth Percentage Index. Our data show that mechanical stress inactivates a CP-containing BT drug, but not a CP-free BT drug. We conclude that CPs do not provide protection against mechanical stress, supporting the view that CPs are not necessary for therapeutic purposes.
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Statistical help of Dr. Leijla Paracka is much appreciated.
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DD received honoraria for services provided to Allergan, Ipsen, Merz, Lanzhou Institute of Biological Products, Medy-Tox, Revance, Desitin, Syntaxin, Abbvie, Medtronic, St Jude, Boston Scientific, Almirall, Bayer, Sun, Teva, UCB, IAB-Interdisciplinary Working Group for Movement Disorders. He is a shareholder of Allergan and holds patents on botulinum toxin and botulinum toxin therapy. LP has nothing to declare. FAS received honoraria for services provided to Abbvie, Almirall, Allergan, Asklepios, Bayer, Desitin, Dynamed, Hempel GesundheitsPartner, Ipsen, Johnson & Johnson, Licher, Meda, Medtronic, Medizinische Hochschule Hannover, Merz, Orion, ParkinsonNet, PTZ Nawrath, Sensomotorik & Rehabilitation Hellmuth & Thiel, Sintetica, Sporlastic, Sun, Teva, Tricumed, TRS Med and UCB. HB has nothing to disclose.
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Dressler, D., Pan, L., Adib Saberi, F. et al. Do complexing proteins provide mechanical protection for botulinum neurotoxins?. J Neural Transm 126, 1047–1050 (2019). https://doi.org/10.1007/s00702-019-02023-x
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DOI: https://doi.org/10.1007/s00702-019-02023-x