The Neuroregenerative Effects of IncobotulinumtoxinA (Inco/A) in a Nerve Lesion Model of the Rat

TL;DR

This study shows that IncobotulinumtoxinA improves nerve recovery in injured rats by promoting regeneration and reducing inflammation.

Contribution

The study demonstrates that IncobotulinumtoxinA, a BoNT/A variant, accelerates nerve regeneration and reduces inflammation in a rat nerve injury model.

Findings

Inco/A treatment improved Sciatic Functional Index by 65% and reduced CMAP onset latency by 22%.

Inco/A-treated rats showed enhanced remyelination and reduced CGRP and S100β expression.

Inco/A reduced immune cell influx by 30%, indicating anti-inflammatory effects aiding nerve recovery.

Abstract

The use of Botulinum Neurotoxin A (BoNT/A) to treat peripheral neuropathic pain from nerve injury has garnered interest for its long-lasting effects and safety. This study examined the effects of IncobotulinumtoxinA (Inco/A), a BoNT/A variant without accessory proteins, on nerve regeneration in rats using the chronic constriction injury (CCI) model. Inco/A was administered perineurally at two time points: on days 0 and 21 post CCI. Functional and histological assessments were conducted to evaluate the effect of Inco/A on nerve regeneration. Sciatic Functional Index (SFI) measurements and Compound Muscle Action Potential (CMAP) recordings were conducted at different time points following CCI. Inco/A-treated animals exhibited a 65% improved SFI and 22% reduction in CMAP onset latencies compared to the vehicle-treated group, suggesting accelerated functional nerve recovery. Tissue analysis revealed enhanced remyelination in Inco/A-treated animals and 60% reduction in CGRP and double S100β signal expression compared to controls. Strikingly, 30% reduced immune cell influx into the injury site was observed following Inco/A treatment, suggesting that its anti-inflammatory effect contributes to nerve regeneration. These findings show that two injections of Inco/A promote functional recovery by enhancing neuroregeneration and modulating inflammatory processes, supporting the hypothesis that Inco/A has a neuroprotective and restorative role in nerve injury conditions.

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