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Electronic Letters to:
- DevelopmentPlasticityRepair:
Flavia Antonucci, Chiara Rossi, Laura Gianfranceschi, Ornella Rossetto, and Matteo Caleo- Long-Distance Retrograde Effects of Botulinum Neurotoxin A
J. Neurosci. 2008; 28: 3689-3696[Abstract] [Full text] [PDF]
eLetters: Submit a response to this article
Electronic letters published:
Is botulinum toxin really moving into the CNS like tetanus toxin?
- K. Roger Aoki, Mitchell F. Brin, Sr. VP & Botox CSO and Scott M. Whitcup, Executive VP, Head R&D (19 April 2008)
Is botulinum toxin really moving into the CNS like tetanus toxin? 19 April 2008 
K. Roger Aoki,
Vice President, Neurotoxins
Allergan 2525 Dupont Drive, Irvine, CA 92623,
Mitchell F. Brin, Sr. VP & Botox CSO and Scott M. Whitcup, Executive VP, Head R&DSend letter to journal:
Re: Is botulinum toxin really moving into the CNS like tetanus toxin?
aoki_roger{at}allergan.com K. Roger Aoki, et al.
The authors claim to provide the first evidence for a mechanism by which botulinum toxin type A (BoNT/A) can access the CNS after peripheral administration (i.e., similar to tetanus toxin). Their data is limited and inconsistent with the literature (Lalli et al, 2003. Trends Microbiol. 11(9):431-437; Tang-Liu et al, 2003. Toxicon 42:461-469). This difference may be explained by several factors (high dose of a research toxin, unreported antibody specificity and lack of reported controls for nonspecific protein transport and detection methodology). The authors administered BoNT/A into a single site of the rat whisker pad (135 pg, ~450 pg/kg). Patients treated with BOTOX® (vs BoNT/A) for facial indications typically receive ~ 20 units (~3 pg/kg) administered into multiple muscles, which is ~150 fold lower than the dose used by the authors. The high dose administered to rats by the authors complicates interpretation of their data by triggering non-specific uptake and overloading the protein transport system of the neuron. The authors published data with an incompletely characterized antibody (sera or purified? controls to differentiate between cleaved/uncleaved SNAP25?) to represent toxin activity in the brain. Their experimental results relied on the appearance of the epitope resulting from cleavage of BoNT/A’s substrate, SNAP25, by western blot (WB) or immunohistochemical (IHC) localization of excised tissues. However, their conclusion of “positive” signal from their uncharacterized antibody as enzymatic activity of BoNT/A in the tissue (WB & IHC) is problematic. Readers should not draw the conclusion that these preliminary non-clinical results are relevant to clinical applications.
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