Evidence map›Paper›PMID 16785105›Full record

ArticleNeurotoxicity research2006

Re-engineering the target specificity of Clostridial neurotoxins - a route to novel therapeutics.

K A Foster, E J Adams, L Durose, C J Cruttwell, E Marks, C C Shone, J A Chaddock, C L Cox, C Heaton, J M Sutton and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Neurotoxicity research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
4.4field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Airway mucus function and dysfunction.The New England journal of medicine · 2010
    Review
  14. Review
  15. Review
  16. Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel.Toxicon : official journal of the International Society on Toxinology · 2009
    Review
  17. Article
  18. Engineering botulinum neurotoxin to extend therapeutic intervention.Proceedings of the National Academy of Sciences of the United States of America · 2009
    Article
  19. Article
  20. Future aspects of botulinum neurotoxins.Journal of neural transmission (Vienna, Austria : 1996) · 2008
    Review
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

13 authors at 3 institutions in 3 countries.

K A FosterHealth Protection Agency, Centre for Emergency Preparedness & Response, Porton Down, Salisbury, UK. keith.foster@hpa.org.uk
E J Adams
L Durose
C J Cruttwell
E Marks
C C Shone
J A Chaddock
C L Cox
C Heaton
J M Sutton
J Wayne
F C G Alexander
D F Rogers
Health Protection Agency · MVNational Institutes of Health · USPublic Health England · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ability to chemically couple proteins to LH(N)-fragments of clostridial neurotoxins and create novel molecules with selectivity for cells other than the natural target cell of the native neurotoxin is well established. Such molecules are able to inhibit exocytosis in the target cell and have the potential to be therapeutically beneficial where secretion from a particular cell plays a causative role in a disease or medical condition. To date, these molecules have been produced by chemical coupling of the LH(N)-fragment and the targeting ligand. This is, however, not a suitable basis for producing pharmaceutical agents as the products are ill defined, difficult to control and heterogeneous. Also, the molecules described to date have targeted neuroendocrine cells that are susceptible to native neurotoxins, and therefore the benefit of creating a molecule with a novel targeting domain has been limited. In this paper, the production of a fully recombinant fusion protein from a recombinant gene encoding both the LH(N)-domain of a clostridial neurotoxin and a specific targeting domain is described, together with the ability of such recombinant fusion proteins to inhibit secretion from non-neuronal target cells. Specifically, a novel protein consisting of the LH(N)-domains of botulinum neurotoxin type C and epidermal growth factor (EGF) that is able to inhibit secretion of mucus from epithelial cells is reported. Such a molecule has the potential to prevent mucus hypersecretion in asthma and chronic obstructive pulmonary disease.

Indexed as

Botulinum ToxinsCell LineEndopeptidasesEpidermal Growth FactorEpithelial CellsEscherichia coliHumansImmunotoxinsLectinsLigandsMucinsProtein EngineeringProtein TransportQa-SNARE ProteinsRecombinant ProteinsRespiratory MucosaBotulinum Toxinsbotulinum toxin type CEndopeptidasesEpidermal Growth FactorImmunotoxinsLectinsLigandsMucinsQa-SNARE ProteinsRecombinant Proteins

Identifiers

PMID16785105
OpenAlexW1543585694

What OpenQuestion holds

Textmetadata
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.