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

Toxins

Flaminia Pavone¹  Sara Marinelli¹  Siro Luvisetto¹  Tiziana Orsini¹  Valentina Vacca¹  PierLorenzo Puri²  Luca Madaro³  FedericaDe Angelis³  Daisy Proietti³  Stefano Cobianchi⁴ 

[1] CNR—National Research Council, Institute of Biochemistry and Cell Biology, 00015 Monterotondo Scalo (RM), Italy;Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA;IRCCS Santa Lucia Foundation, 00143 Roma, Italy;Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Spain;

关键词: botulinum neurotoxin type A;    glial scar;    spinal cord injury;    neuropathic pain;    neurodegeneration;    paralysis;   

DOI  :  10.3390/toxins12080491

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown