scholarly journals Botulinum neurotoxin A for chronic migraine headaches: does it work and how?

2014 ◽  
Vol 4 (6) ◽  
pp. 377-380 ◽  
Author(s):  
Brian E Cairns ◽  
Parisa Gazerani
Keyword(s):  
Chronic Migraine ◽  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A ◽  
Migraine Headaches

scholarly journals Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Botulinum Neurotoxin a in the Preventive Treatment of Chronic Migraine: An Adjusted Indirect Treatment Comparison Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yao-Yao Chen ◽  
Xiao-Qian Ye ◽  
Tai-Chun Tang ◽  
Tian-Wei She ◽  
Min Chen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Migraine ◽  
Botulinum Neurotoxin ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Controlled Trials ◽  
Botulinum Neurotoxin A ◽  
Related Peptide ◽  
Calcitonin Gene

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis.Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score.Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate.Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

scholarly journals Botulinum Neurotoxin A Prevents the Development of Nitroglycerin-Induced Chronic Migraine via Inhibition of CGRP and NLRP3 Inflammasomes in Mice

2020 ◽  
Author(s):  
Ting Zhu ◽  
Jing-Qi Niu ◽  
Cun-Jin Su ◽  
Jia-Wei Chen ◽  
Yan-Lin Zhang ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Western Blotting ◽  
Botulinum Neurotoxin ◽  
Preventive Treatment ◽  
Repeated Administration ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
Botulinum Neurotoxin A ◽  
Mechanical Hypersensitivity ◽  
Nlrp3 Inflammasomes

Abstract Background This study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on chronic migraine and to explore the potential mechanisms by using a mouse model of chronic migraine, which was established by repeated intraperitoneal (i.p.) injection with nitroglycerin (NTG).Methods NTG-induced basal and evoked mechanical hypersensitivity were evaluated using the von Frey filament test. Before the first injection of NTG, a single facial injection of BoNT/A was administered in the supraorbital region to explore its preventive effects on the development of chronic migraine in mice. The expression of calcitonin gene-related peptide (CGRP) and synaptosomal-associated protein25 (SNAP25) in the trigeminal ganglia (TG) and the trigeminal nucleus caudalis (TNC) were detected by Western blotting and immunostaining. Results Repeated administration of NTG resulted in basal and evoked mechanical hypersensitivity in mice. Single facial BoNT/A injection prevented the development of NTG-induced mechanical hypersensitivity in mice. Western blotting results revealed that peripheral BoNT/A injection decreased the NTG-induced upregulation of expression of CGRP and SNAP25 in the TGs and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes in the TNC. Immunostaining results revealed peripheral BoNT/A injection also decreased the NTG-induced upregulation of CGRP expression in the TNC.Conclusions Thus, these results indicate that single facial injection of BoNT/A may be a preventive treatment of chronic migraine, possible due to the inhibitory effect of BoNT/A on the expression of CGRP and SNAP25 in the TGs and NLRP3 inflammasomes in the TNC.

scholarly journals Effectiveness of botulinum neurotoxin A, topiramate, and acupuncture in preventive treatment of chronic migraine: a network meta-analysis

2020 ◽  
Author(s):  
Hui Zheng ◽  
Shi-Le Huang ◽  
Yao-Yao Chen ◽  
Tai-Chun Tang ◽  
Di Qin ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Migraine ◽  
Botulinum Neurotoxin ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Risk Of Bias ◽  
Adverse Event Rate ◽  
Controlled Trials ◽  
Botulinum Neurotoxin A ◽  
Standard Mean Difference

Abstract Background Botulinum neurotoxin A (BoNT-A) was the primary choice for preventive treatment of chronic migraine. Topiramate and acupuncture showed promising effect for the condition, but their effectiveness relative to BoNT-A was rarely studied. We aimed to perform a network meta-analysis to compare the effectiveness and acceptability between BoNT-A, topiramate, and acupuncture.Methods We searched OVID Medline, Embase, the Cochrane register of controlled trials (CENTRAL), the Chinese Clinical Trial Register, and clinicaltrials.gov for randomized controlled trials (RCTs) that compared BoNT-A, topiramate, and acupuncture with any of them or placebo in the preventive treatment of chronic migraine. Two independent reviewers screened RCTs, extracted data, and assessed risk of bias. A network meta-analysis was performed by using a frequentist approach and a random-effects model. The primary outcomes were reduction in monthly headache days and monthly migraine days at week 12. Acceptability was assessed by adverse event rate. The effect size of the primary outcomes was measured by using standard mean difference (SMD).Results We included 15 RCTs (n = 2545). Eleven RCTs were at low risk of bias. The network meta-analyses (n = 2061) showed that acupuncture (2061 participants; SMD − 1.61, 95%CI -2.35 to -0.87) and topiramate(582 participants; SMD − 0.4, 95%CI -0.75 to -0.04) ranked the most effective in the reduction of monthly headache days and migraine days, respectively; but they were not significantly superior over BoNT-A. Topiramate caused the most treatment-related adverse events and the highest rate of dropouts owing to adverse events.Conclusions Topiramate and acupuncture were not superior over BoNT-A. In terms of acceptability and accessibility of treatments, BoNT-A was still the primary choice for preventive treatment of chronic migraine.

Identification of novel inhibitors of botulinum neurotoxin A

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
C Yalamanchili ◽  
VK Manda ◽  
AG Chittiboyina ◽  
WA Harrell Jr ◽  
RP Webb ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

2017 ◽  
Vol 36 (05) ◽  
pp. 315-323
Author(s):  
N. Üçeyler ◽  
C. Sommer
Keyword(s):  
Botulinum Neurotoxin ◽  
Neuropathische Schmerzen ◽  
Botulinum Neurotoxin A ◽  
Topische Therapien

ZusammenfassungDie Behandlung neuropathischer Schmerzen mit systemisch wirksamen oral verabreichten Pharmaka ist bei vielen Patienten wirksam, kann jedoch zu zentralnervösen unerwünschten Wirkungen wie Müdigkeit oder Schwindel führen. Daher sind in den letzten Jahren topische Therapien in das Zentrum der Aufmerksamkeit gerückt. Botulinumtoxin, etabliert in der Therapie von Dystonien und Spastik, wurde zunehmend bei Schmerzerkrankungen getestet, hierbei ist Botulinum-Neurotoxin A der am besten untersuchte Serotyp. Die häufigsten Indikationen waren Schmerzen im Trigeminusversorgungsbereich und periphere neuropathische Schmerzen. Bei den meisten Studien war Botulinum-Neurotoxin A Placebo deutlich überlegen. Präklinische Studien zum Wirkmechanismus erbrachten die Erkenntnis, dass neben dem erwarteten peripheren Effekt sehr wahrscheinlich auch eine zentrale Reduktion der Ausschüttung von exzitatorischen Neurotransmittern an der Wirkung beteiligt ist.

scholarly journals Primary Cultures of Embryonic Chicken Neurons for Sensitive Cell-Based Assay of Botulinum Neurotoxin: Implications for Therapeutic Discovery

2007 ◽  
Vol 12 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Andrea M. Stahl ◽  
Gordon Ruthel ◽  
Edna Torres-Melendez ◽  
Tara A. Kenny ◽  
Rekha G. Panchal ◽  
...  
Keyword(s):  
Nervous System ◽  
Botulinum Toxin ◽  
Neutralizing Antibodies ◽  
Botulinum Neurotoxin ◽  
Potent Inhibitor ◽  
Primary Cultures ◽  
Embryonic Chick ◽  
Sensitive Cell ◽  
Botulinum Neurotoxin A ◽  
Therapeutic Compounds

Botulinum toxin is an exceedingly potent inhibitor of neurotransmission across the neuromuscular junction, causing flaccid paralysis and death. The potential for misuse of this deadly poison as a bioweapon has added a greater urgency to the search for effective therapeutics. The development of sensitive and efficient cell-based assays for the evaluation of toxin antagonists is crucial to the rapid and successful identification of therapeutic compounds. The authors evaluated the sensitivity of primary cultures from 4 distinct regions of the embryonic chick nervous system to botulinum neurotoxin A (BoNT/A) cleavage of synaptosomal-associated protein of 25 kD (SNAP-25). Although differences in sensitivity were apparent, SNAP-25 cleavage was detectable in neuronal cells from each of the 4 regions within 3 h at BoNT/A concentrations of 1 nM or lower. Co-incubation of chick neurons with BoNT/A and toxin-neutralizing antibodies inhibited SNAP-25 cleavage, demonstrating the utility of these cultures for the assay of BoNT/A antagonists. ( Journal of Biomolecular Screening 2007:370-377)

scholarly journals Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Changjiao Gan ◽  
Wenbo Luo ◽  
Yunzhou Yu ◽  
Zhouguang Jiao ◽  
Sha Li ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Clostridium Botulinum ◽  
Freeze Drying ◽  
Botulinum Neurotoxin ◽  
Secretory Iga ◽  
Immune Protection ◽  
Dry Powder ◽  
Botulinum Neurotoxin A ◽  
Spray Freeze Drying

AbstractBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

scholarly journals Strategies to Counteract Botulinum Neurotoxin A: Nature’s Deadliest Biomolecule

2019 ◽  
Vol 52 (8) ◽  
pp. 2322-2331 ◽  
Author(s):  
Lucy Lin ◽  
Margaret E. Olson ◽  
Lisa M. Eubanks ◽  
Kim D. Janda
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A

Covalent inhibition of botulinum neurotoxin A – Exploration of warhead reactivity and function using a bifunctional approach

Toxicon ◽  
2021 ◽  
Vol 190 ◽  
pp. S72-S73
Author(s):  
Lewis D. Turner ◽  
Alexander L. Nielsen ◽  
Lucy Lin ◽  
Sabine Pellett ◽  
Takashi Sugane ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A ◽  
Covalent Inhibition ◽  
And Function
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