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© Emmanuel Lemichez
Microscopy image showing the formation of large tunnels in a blood vessel endothelial cell induced by a group of bacterial toxins
Publication : Toxicon : official journal of the International Society on Toxinology

Phrenic nerve-hemidiaphragm as a highly sensitive replacement assay for determination of functional botulinum toxin antibodies

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Toxicon : official journal of the International Society on Toxinology - 13 Apr 2011

Rasetti-Escargueil C, Liu Y, Rigsby P, Jones RG, Sesardic D

Link to Pubmed [PMID] – 21513727

Toxicon 2011 Jun;57(7-8):1008-16

Botulinum neurotoxins induce a prolonged muscle paralysis by specifically blocking the release of neuronal transmitters from peripheral nerve junctions. Potency testing of toxin and antitoxin therapies is entirely dependent on mouse lethality bioassay which is associated with extreme suffering of large numbers of animals to ensure high precision. The mouse phrenic nerve-diaphragm assay is an ex vivo assay that closely mimics in vivo respiratory paralysis offering substantial refinement and reduction in the number of animals used. A range of botulinum antitoxin standards, one licenced product and experimental antitoxins were tested for neutralising potency using ex vivo hemidiaphragm assay and compared with in vivo determined activities. Overall, there was an excellent agreement between neutralising activity detected by the two assay systems and for each toxin serotype using only 4-7 replicates for each product (almost perfect concordance for type A antitoxins: ρ = 0.997, and substantial concordance for type B antitoxins: ρ = 0.991 and type E antitoxins: ρ = 0.964, respectively). These findings confirm that the mouse nerve-diaphragm preparation can provide a functional ex vivo replacement assay for specific, sensitive and precise assessment of toxin and antitoxin activity.

https://www.ncbi.nlm.nih.gov/pubmed/21513727