Traditionally
the potency of botox has been evaluated using the LD50 test. These tests cause
immense suffering to the animals involved and are expensive in terms of the
animals and resources required for carrying them out. Because of this a number
of alternatives to the LD50 test are being developed, with perhaps the most
hopeful being the SNAP-25 assay:
SNAP-25 is a protein involved in nerve signalling. Botox binds to SNAP-25 splicing
it in half and preventing it from carrying out its normal function. This results
in localised paralysis and the removal of wrinkles. As SNAP-25 is the primary
target of Botox, directly measuring the effect of the toxin on this protein
provides a far more specific and efficient method for measuring potency than
the LD50 test. To measure how much SNAP-25 protein is cleaved by a particular
batch of Botox, synthetic SNAP-25 peptides are used, which when cleaved fluoresce.
Following exposure to the Botox the amount of flourescence emitted by the claeved
SNAP-25 protein is directly proportional to the potency of the Botox. By using
different dilutions of the Botox this method can allow for the simple calculation
of LD50-equivalent values.
The government-funded lab at the National Institute for Biological Standards
and Control now use the SNAP-25 endopeptidase assay for routine batch-release
confirmation. It has been described as sensitive, technically simple, rapid
and also provides less inter-laboratory variability. The method is still being
improved and it is hoped that in the near future the use of this method in combination
with an ELISA in vitro assay technique that directly measures the concentration
of Botox toxin in a batch sample, as well as an international reference standard
for Botox, will soon end the need for the LD50 test to be used for cosmetic
Botox batch-testing.