Evidence map›Paper›PMID 22069712›Full record

ArticleToxins2011

Re-assembled botulinum neurotoxin inhibits CNS functions without systemic toxicity.

Enrico Ferrari, Elizabeth S Maywood, Laura Restani, Matteo Caleo, Marco Pirazzini, Ornella Rossetto, Michael H Hastings, Dhevahi Niranjan, Giampietro Schiavo, Bazbek Davletov

Open access · goldAbstract read
In one paragraph

Article in Toxins, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
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  6. Astrocytic control of extracellular GABA drives circadian timekeeping in the suprachiasmatic nucleus.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Review
  8. Review
  9. Novel Native and Engineered Botulinum Neurotoxins.Handbook of experimental pharmacology · 2021
    Review
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  11. Article
  12. Review
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  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Enrico FerrariMedical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. eferrari@mrc-lmb.cam.ac.uk
Elizabeth S Maywood
Laura Restani
Matteo Caleo
Marco Pirazzini
Ornella Rossetto
Michael H Hastings
Dhevahi Niranjan
Giampietro Schiavo
Bazbek Davletov
MRC Laboratory of Molecular Biology · GBNeuroscience Institute · ITUniversity of Padua · ITCancer Research UK · GBMedical Research Council · GB

Funding

Medical Research Council MC_U105170643Medical Research Council MC_U105178791
6 · The paper itself

Abstract

The therapeutic potential of botulinum neurotoxin type A (BoNT/A) has recently been widely recognized. BoNT/A acts to silence synaptic transmission via specific proteolytic cleavage of an essential neuronal protein, SNAP25. The advantages of BoNT/A-mediated synaptic silencing include very long duration, high potency and localized action. However, there is a fear of possible side-effects of BoNT/A due to its diffusible nature which may lead to neuromuscular blockade away from the injection site. We recently developed a "protein-stapling" technology which allows re-assembly of BoNT/A from two separate fragments. This technology allowed, for the first time, safe production of this popular neuronal silencing agent. Here we evaluated the re-assembled toxin in several CNS assays and assessed its systemic effects in an animal model. Our results show that the re-assembled toxin is potent in inhibiting CNS function at 1 nM concentration but surprisingly does not exhibit systemic toxicity after intraperitoneal injection even at 200 ng/kg dose. This shows that the re-assembled toxin represents a uniquely safe tool for neuroscience research and future medical applications.

Indexed as

AnimalsBotulinum Toxins, Type ACentral Nervous SystemDisease Models, AnimalGene Expression RegulationImmunoblottingLuminescent MeasurementsMiceMice, Inbred C57BLNeuronsNeurotoxinsRatsSynaptic TransmissionSynaptosomal-Associated Protein 25Botulinum Toxins, Type ANeurotoxinsSnap25 protein, ratSynaptosomal-Associated Protein 25BITOXBOTOXbotulinum neurotoxinnervous systemprotein engineeringSNAREssynapse

Identifiers

PMID22069712
PMCPMC3202830
OpenAlexW2131201034

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.