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Open AccessArticle

Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice

1
CNR—National Research Council, Institute of Biochemistry and Cell Biology, 00015 Monterotondo Scalo (RM), Italy
2
IRCCS Santa Lucia Foundation, 00143 Roma, Italy
3
DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy
4
Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Spain
5
Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
*
Authors to whom correspondence should be addressed.
To be considered as senior authors.
Toxins 2020, 12(8), 491; https://doi.org/10.3390/toxins12080491
Received: 10 June 2020 / Revised: 27 July 2020 / Accepted: 28 July 2020 / Published: 31 July 2020
Botulinum neurotoxin type A (BoNT/A) is a major therapeutic agent that has been proven to be a successful treatment for different neurological disorders, with emerging novel therapeutic indications each year. BoNT/A exerts its action by blocking SNARE complex formation and vesicle release through the specific cleavage of SNAP-25 protein; the toxin is able to block the release of pro-inflammatory molecules for months after its administration. Here we demonstrate the extraordinary capacity of BoNT/A to neutralize the complete paralysis and pain insensitivity induced in a murine model of severe spinal cord injury (SCI). We show that the toxin, spinally administered within one hour from spinal trauma, exerts a long-lasting proteolytic action, up to 60 days after its administration, and induces a complete recovery of muscle and motor function. BoNT/A modulates SCI-induced neuroglia hyperreactivity, facilitating axonal restoration, and preventing secondary cells death and damage. Moreover, we demonstrate that BoNT/A affects SCI-induced neuropathic pain after moderate spinal contusion, confirming its anti-nociceptive action in this kind of pain, as well. Our results provide the intriguing and real possibility to identify in BoNT/A a therapeutic tool in counteracting SCI-induced detrimental effects. Because of the well-documented BoNT/A pharmacology, safety, and toxicity, these findings strongly encourage clinical translation. View Full-Text
Keywords: botulinum neurotoxin type A; glial scar; spinal cord injury; neuropathic pain; neurodegeneration; paralysis; regeneration botulinum neurotoxin type A; glial scar; spinal cord injury; neuropathic pain; neurodegeneration; paralysis; regeneration
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MDPI and ACS Style

Vacca, V.; Madaro, L.; De Angelis, F.; Proietti, D.; Cobianchi, S.; Orsini, T.; Puri, P.L.; Luvisetto, S.; Pavone, F.; Marinelli, S. Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice. Toxins 2020, 12, 491. https://doi.org/10.3390/toxins12080491

AMA Style

Vacca V, Madaro L, De Angelis F, Proietti D, Cobianchi S, Orsini T, Puri PL, Luvisetto S, Pavone F, Marinelli S. Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice. Toxins. 2020; 12(8):491. https://doi.org/10.3390/toxins12080491

Chicago/Turabian Style

Vacca, Valentina; Madaro, Luca; De Angelis, Federica; Proietti, Daisy; Cobianchi, Stefano; Orsini, Tiziana; Puri, Pier L.; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara. 2020. "Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice" Toxins 12, no. 8: 491. https://doi.org/10.3390/toxins12080491

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