Botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human

Arg206 of SNAP-25 is essential for neuroexocytosis at the Drosophila melanogaster neuromuscular junction

“…Although further analysis with expression of the mutant SNAP-25 in a null background is required to substantiate the present results, the consistency of the data reported here suggests that the presence of a single mutant SNARE complex in the very critical region of protein-protein contact between the petals of the rosette is sufficient to block the activity of the rosette. This does explain the dominantnegative nature of the mutation introduced here with respect to neuroexocytosis, and fits well with the specific action of BoNT/A and BoNT/C which cleave SNAP-25 just before and after Arg198, respectively, causing a dominant-negative effect with the characteristic long duration of action of these two neurotoxins (Eleopra et al, 1997;Eleopra et al, 1998;Meunier et al, 2003). The present model also explains the remarkable findings that the replacements of Lys201 and Leu203 with a negatively charged glutamate residue do not affect SNARE assembly but inhibits exocytosis in chromaffin cells (Criado et al, 1999;Gil et al, 2002) as these changes are disturbing the protein-protein contacts between adjacent SNARE complexes.…”

Evaluation of the Therapeutic Usefulness of Botulinum Neurotoxin B, C1, E, and F Compared with the Long Lasting Type A

“…Therefore, an alternative serotype with the potency and duration of type A is required. In this context, these studies have demonstrated that BoNT/C1 may possess such therapeutic potential (17), except that it has been reported to impair neurite/axonal growth and cause cell death, an effect not ascribable to contamination (Ref . 20 and this work).…”

“…14), BoNT/A, BoNT/B, and BoNT/E cause neuromuscular paralysis for more than 4 months, ϳ2 months, or Ͻ4 weeks, respectively (15,16); the limited results available for type C1 suggest a duration less than or equal to that of BoNT/A (17). It is unclear why the recovery times in rodents are shorter and yet show the same rank order (1-2 months (BoNT/A), 21 days (BoNT/B), 7 days (BoNT/F), and 4 days (BoNT/E)) (18,19).…”

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia

“…When clinical non-response occurs, other botulinum toxin serotypes are important treatment options for cervical dystonia (Cullis 2000;Eleopra 1997;Greene 1993 …”