In-vivo comparison of the neurotoxic potencies of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA.
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 2μl) was studied in four groups of mice (n=13-15). The potencies of the BoNT products were then compared by injecting identical volumes (10μl) 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.
Department of Clinical Neurophysiology, University Medical Centre Göttingen, Göttingen, Germany. Electronic address: anna.kutschenko@med.uni-goettingen.de.
Anna
A
Kutschenko
Department of Clinical Neurophysiology, University Medical Centre Göttingen, Göttingen, Germany.
Anja
A
Manig
Department of Clinical Neurophysiology, University Medical Centre Göttingen, Göttingen, Germany.
Marie-Christine
MC
Reinert
Department of Clinical Neurophysiology, University Medical Centre Göttingen, Göttingen, Germany.
Angelika
A
Mönnich
Department of Clinical Neurophysiology, University Medical Centre Göttingen, Göttingen, Germany.
David
D
Liebetanz
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D010291:Paresis / Q000139:chemically induced*
D009498:Neurotoxins; D019274:Botulinum Toxins, Type A; C542869:abobotulinumtoxinA; C545476:incobotulinumtoxinA
AbobotulinumtoxinA; IncobotulinumtoxinA; Neurotoxic potency; OnabotulinumtoxinA; Volume-dependency; Wheel-running performance