-
Is botulinum toxin really moving into the CNS like tetanus toxin?
Submit responseThe 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.
- Print ISSN: 0270-6474
- Online ISSN: 1529-2401
