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.

Revealing the therapeutic potential of botulinum neurotoxin type a in counteracting paralysis and neuropathic pain in spinally injured mice / Vacca, V.; Madaro, L.; De Angelis, F.; Proietti, D.; Cobianchi, S.; Orsini, T.; Puri, P. L.; Luvisetto, S.; Pavone, F.; Marinelli, S.. - In: TOXINS. - ISSN 2072-6651. - 12:8(2020), pp. 1-30. [10.3390/toxins12080491]

Revealing the therapeutic potential of botulinum neurotoxin type a in counteracting paralysis and neuropathic pain in spinally injured mice

Vacca V.;Madaro L.;Cobianchi S.;Pavone F.;
2020

Abstract

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.
2020
botulinum neurotoxin type A; glial scar; neurodegeneration; neuropathic pain; paralysis; regeneration; spinal cord injury
01 Pubblicazione su rivista::01a Articolo in rivista
Revealing the therapeutic potential of botulinum neurotoxin type a in counteracting paralysis and neuropathic pain in spinally injured mice / Vacca, V.; Madaro, L.; De Angelis, F.; Proietti, D.; Cobianchi, S.; Orsini, T.; Puri, P. L.; Luvisetto, S.; Pavone, F.; Marinelli, S.. - In: TOXINS. - ISSN 2072-6651. - 12:8(2020), pp. 1-30. [10.3390/toxins12080491]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1470696
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