A comparison study of prabotulinumtoxinA vs onabotulinumtoxinA in myostatin-deficient mice with muscle hypertrophy

Basic Clin Pharmacol Toxicol. 2019 Apr;124(4):491-499. doi: 10.1111/bcpt.13151. Epub 2018 Nov 8.

Abstract

Botulinum toxin A (BoNT-A) is used clinically for various muscle disorders and acts by preventing the release of the neurotransmitter acetylcholine into the synapse space. Here, we compared the efficacy of prabotulinumtoxinA (PRA) and onabotulinumtoxinA (ONA) for the reduction in hypertrophy in myostatin-deficient (Mstn-/- ) mice. Two different BoNT-A products (2.5, 10 and 25 U/kg) were injected to paralyse the hindlimb for 2 months, after which sciatic nerve conduction study, 3D micro-CT, haematoxylin and eosin (H&E) and dystrophin staining were conducted. Administration of BoNT-A products induced denervation-mediated atrophy and alleviated muscle hypertrophy generated in Mstn-/- mice. The present study revealed that each BoNT-A regulates skeletal muscle size, myofibre number and myofibre diameter in Mstn-/- mice. The potential applicability of BoNT-A for the treatment of rare muscle hypertrophic diseases was demonstrated. Compared with ONA, PRA had a comparable ability to act in the local area.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Botulinum Toxins / administration & dosage
  • Botulinum Toxins / pharmacology*
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hindlimb
  • Hypertrophy / drug therapy*
  • Hypertrophy / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / pathology
  • Muscular Diseases / drug therapy*
  • Muscular Diseases / physiopathology
  • Myostatin / genetics*
  • Neuromuscular Agents / administration & dosage
  • Neuromuscular Agents / pharmacology

Substances

  • Mstn protein, mouse
  • Myostatin
  • Neuromuscular Agents
  • prabotulinumtoxin A
  • Botulinum Toxins
  • Botulinum Toxins, Type A
  • onabotulinum toxin A

Supplementary concepts

  • Myostatin-related muscle hypertrophy