In-vivo comparison of the neurotoxic potencies of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA. (3rd August 2016)

• Record Type: Journal Article
• Authors: Kutschenko, Anna; Manig, Anja; Reinert, Marie-Christine; Mönnich, Angelika; Liebetanz, David
• Is Part Of: Neuroscience letters. Volume 627(2016)
• Page Start: 216
• Page End: 221
• Publication Date: 2016-08-03
• Subjects: BoNT botulinum neurotoxin -- BoNT/A-G botulinum neurotoxin type A-G -- A/Inco incobotulinumtoxinA (Xeomin®) -- A/Ona onabotulinumtoxinA (Botox®) -- A/Abo abobotulinumtoxinA (Dysport®) -- DAS assay digit abduction score assay -- MU mouse unit -- Vmax maximum running velocity -- ANOVA analysis of variance; IncobotulinumtoxinA -- OnabotulinumtoxinA -- AbobotulinumtoxinA -- Volume-dependency -- Neurotoxic potency -- Wheel-running performance; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.06.001
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: IncobotulinumtoxinA, onabotulinumtoxinA, abobotulinumtoxinA are not interchangeable. The same number of mouse units induces different degrees of paresis. OnabotulinumtoxinA is relevantly more potent than incobotulinumtoxinA. The potency of onabotulinumtoxinA is two-fold greater than of abobotulinumtoxinA. The same value of paresis also results in an identical duration of paresis. Abstract: Three botulinum neurotoxin type A (BoNT/A) products, incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA, all manufactured by different methods, are employed in clinical practice. Comparing the three BoNT/A products is difficult because their concentrations and volumes differ and the precise dose equivalence ratio is not known. We aimed to compare the neurotoxic potencies by a systematic analysis of injected volume and dose. The potency of BoNT in inducing hind limb paresis was assessed by analyzing the wheel-running performance of mice. To standardize the volume, the effect of an identical dose of incobotulinumtoxinA dissolved in different volumes of saline (15, 10, 5, and 2 μl) was studied in four groups of mice (n = 13–15). The potencies of the BoNT products were then compared by injecting identical volumes (10 μl) containing different doses into both hind leg muscles. Mice injected with incobotulinumtoxinA showed a volume-dependent reduction in wheel-running, with larger volumes inducing more intense paresis. A standardized volume containing the same number of mouse units of the BoNT/A products produced different degrees of paresis. The conversion ratio of incobotulinumtoxinA and onabotulinumtoxinA is estimated to be between 1:0.75 and 1:0.5. OnabotulinumtoxinA displayed a two-fold greater potency than abobotulinumtoxinA. Doses of onabotulinumtoxinA and abobotulinumtoxinA that produce an identical severity of pareses even result in the same duration of pareses. This wheel-running assay allows one to compare the neurotoxic potency of different volumes and doses of the BoNT products in vivo . Our results argue against common clinical practice because incobotulinumtoxinA and onabotulinumtoxinA are not readily interchangeable and a two-fold dose of abobotulinumtoxinA is needed to induce an effect identical to onabotulinumtoxinA. In addition, this emphasizes that the duration of BoNT-induced effect is the same as long as equipotent doses of BoNT are injected.