Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models

Colin K. Franz*, Alyssa Puritz, Lewis A. Jordan, Jeffrey Chow, J. Alberto Ortega, Evangelos Kiskinis, Charles J. Heckman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background. Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy. A pharmacological means to re-produce the CLE is highly desirable. Objective. To test whether chemodenervation with a clinical grade formulation of botulinum toxin A (BoTX) would be sufficient to reproduce the CLE. Methods. We examined the effects of a 1-week preconditioning administration of BoTX on motor axon regrowth in both a mouse tibial nerve injury and human embryonic stem cell (hESC)–based model. We assessed neuronal reinnervation in vivo (mice) with retrograde tracers and histological analysis of peripheral nerve tissue after injections into the triceps surae muscle group. We assessed motor neuron neurite outgrowth in vitro (hESC) after incubation in BoTX by immunohistochemistry and morphometric analysis. Results. We found that BoTX conditioning treatment significantly enhanced outgrowth of both murine motor axons in vivo and human MN neurites in vitro. Conclusions. BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.

Original languageEnglish (US)
Pages (from-to)735-745
Number of pages11
JournalNeurorehabilitation and Neural Repair
Volume32
Issue number8
Early online dateJul 25 2018
DOIs
StatePublished - Aug 1 2018

Keywords

  • axon regeneration
  • botulinum toxin
  • human embryonic stem cell
  • motor neuron
  • nerve transfer
  • neurite regrowth
  • neuromuscular junction
  • peripheral nerve injury
  • regenerative rehabilitation
  • stem cell derived–motor neuron

ASJC Scopus subject areas

  • Rehabilitation
  • Neurology
  • Clinical Neurology

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