Session Information
Date: Tuesday, September 24, 2019
Session Title: Dystonia
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To quantify the amount of botulinum neurotoxin-A (BoNT-A) protein in each vial of commercial BoNT-A product and compare light chain activity of 150 kDa BoNT-A in different products.
Background: Therapeutic BoNT-A effects are mediated by the 150 kDa neurotoxin. Each product has a unique manufacturing process, different excipients, potency units and dosing recommendations. For example, in Canada (where clearly defined maximum dosing recommendations are provided for all 3 products), the maximum total dose for use in cervical dystonia (CD) is 1000U for abobotulinumtoxinA (aboBoNT-A, Dysport), 360U for onabotulinumtoxinA (onaBoNT-A, Botox), and 300U for incobotulinumtoxinA (incoBoNT-A, Xeomin). Light chain activity of 150 kDa BoNT-A in different products is unknown.
Method: Quantitation of 150 kDa BoNT-A used sandwich ELISA with antibodies specific to 150 kDa BoNT-A. Commercial products were quantitated versus a calibration curve of recombinant BoNT-A. Activity was assessed using EndoPep assay. Concentration of a cleaved target was measured and quantity of 150 kDa BoNT-A determined relative to quantity of recombinant BoNT-A required for equivalent light chain activity.
Results: The amount of 150 kDa neurotoxin per potency unit of commercial product was 5.38pg for aboBoNT-A, 9.04pg for onaBoNT-A and 4.03pg for incoBoNT-A. Thus, when total recommended CD doses are given, there is more 150 kDa BoNT-A injected in aboBoNT-A (1000U x 5.38pg = 5.38ng) than in onaBoNT-A (360U x 9.04pg = 3.25ng) and incoBoNT-A (300U x 4.03 = 1.21ng). Similar results are found at recommended initial doses (aboBoNT-A 500U = 2.69ng vs. onaBoNT-A 200U = 1.81ng vs. incoBoNT-A 200U = 0.81ng). EndoPep assay showed no significant differences between BoNT-A products in light chain activity per ng of 150 kDa toxin.
Conclusion: No differences in light chain activity were seen between BoNT-A products. However, there were greater amounts of neurotoxin in aboBoNT-A at the maximum total dose than either onaBoNT-A or incoBoNT-A. At the recommended dose, all BoNT-A products have a similar safety profile. This greater amount of neurotoxin may prolong denervation following aboBoNT-A injection, resulting in the previously observed clinically long duration of response with sustained symptom relief between injections.
To cite this abstract in AMA style:
M. Field, A. Splevins, M. Schans, J. Langenberg, D. Noort, P. Picaut, K. Foster. Botulinum toxin content and activity: Potential implications for duration of efficacy in patients with cervical dystonia [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/botulinum-toxin-content-and-activity-potential-implications-for-duration-of-efficacy-in-patients-with-cervical-dystonia/. Accessed November 24, 2024.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/botulinum-toxin-content-and-activity-potential-implications-for-duration-of-efficacy-in-patients-with-cervical-dystonia/