Objective: This study aims to compare the neurotoxic potency of four different kinds of toxins, accompanied with expression level changes of key factors after BoNT/A treatment.

Background: Botulinum toxins are the most toxic exotoxins widely used for clinical diseases including neuromuscular diseases. Four botulinumtoxins type A (BoNT/A) formulations, onabotulinumtoxinA (A/Ona, Botox), incobotulinumtoxinA (A/Inco, Xeomin), BotulinumtoxinA (BTA) and Botulinum Neurotoxin type A (BNT-A, 150KD) are applied in the present study among which BNT-A is newly produced. All four preparations are manufactured via different methods and demonstrate unique features, making them not interchangeable.

Methods: 189 male Sprague-Dawley rats  were randomized to injection with onabotulinumtoxinA, incobotulinumtoxinA, BotulinumtoxinA, or Botulinum Neurotoxin type A in  the gastrocnemius. Muscle strength  were measured at 1w, 4w, and 12w after injection. Fresh muscles were harvested simultaneously at each specific time point for the detection of key factors associated with neuromuscular junction formation. In addition, fluorescent staining of histological frozen sections were used to investigate the effect of four kinds of toxins on AChR clustering after injection.

Results: Muscle strength of all four toxins reduced significantly 7 days after BoNT/A administration among which BNT-A achieved the most decrease. This reduction was gradually recovered due to wore-off of toxins and increase of body weight, and no obvious difference was observed 12 weeks after toxins injection. Accordingly, genes including nicotinic acetylcholine receptor (nAChR), Myogenic regulatory factors (MRFs) and muscle-specific receptor tyrosine kinase (MuSK) were up-regulated after BoNT/A injection. BNT-A induced the most significant up-regulation of genes expression. We also found local inflammation response following BoNT/A administration. Due to the lack of complexing proteins, both A/Inco and BNT-A stimulated a relatively less inflammation response comparing to A/Ona and BTA formulations.

Conclusions: we demonstrated that BoNT/A injection had a significant role in inducing muscle paralysis, accompanied with induction of key factors. Due to the different characterizes of the four botulinum toxin A formulations, they presented specific toxic potency in inducing muscle paralysis and key factors expression.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/comparison-of-neurotoxic-potency-of-a-newly-produced-botulinum-neurotoxin-type-a-with-onabotulinumtoxina-incobotulinumtoxina-and-botulinumtoxina/