Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice
Vacca, Valentina (IRCCS Santa Lucia Foundation (Roma, Itàlia))
Madaro, Luca (Università degli Studi di Roma "La Sapienza")
De Angelis, Federica (IRCCS Santa Lucia Foundation (Itàlia))
Proietti, Daisy (Università degli Studi di Roma "La Sapienza")
Cobianchi, Stefano (Universitat Autònoma de Barcelona. Institut de Neurociències)
Orsini, Tiziana (CNR-National Research Council (Itàlia))
Puri, Pier Lorenzo (Sanford Burnham Prebys Medical Discovery Institute (Estats Units d'Amèrica))
Luvisetto, Siro (CNR-National Research Council (Itàlia))
Pavone, Flaminia (IRCCS Santa Lucia Foundation (Itàlia))
Marinelli, Sara (IRCCS Santa Lucia Foundation (Itàlia))

Fecha:	2020
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Botulinum neurotoxin type A ; Glial scar ; Spinal cord injury ; Neuropathic pain ; Neurodegeneration ; Paralysis ; Regeneration
Publicado en:	Toxins, Vol. 12 (july 2020) , ISSN 2072-6651

DOI: 10.3390/toxins12080491
PMID: 32751937

30 p, 17.9 MB

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