Search Results (3)

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24–27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule. Full article

Background: Botulinum neurotoxin is widely regarded as a “wonder medicine” due to its therapeutic efficacy in treating a variety of conditions. While it is traditionally classified as a neurotoxin, it is arguably more appropriate to refer to it as a neuromedicine. All FDA-approved formulations of botulinum neurotoxin are currently administered through intramuscular injections, with no other delivery methods widely used. The primary reasons for this include the following: (a) the extremely high potency of the toxin, (b) the potential for diffusion to adjacent muscles, (c) factors related to the site of administration (e.g., muscle thickness), (d) the large size of the molecule, (e) the impermeability of skin to large protein molecules, and (f) safety concerns. Despite these challenges, there is growing interest in the development of an effective transdermal formulation of botulinum neurotoxin. Refining and standardizing the delivery technology for topical or transdermal use remains an important goal for the future. Methods: The aim of this study was to develop a nanoemulsion-based transdermal formulation capable of delivering active botulinum neurotoxin (BoNT) through human skin. The goal was to demonstrate its efficacy in a mouse model, highlighting the therapeutic effects on both neuromuscular activity and hyperhidrosis. We successfully developed a nanoemulsion-based formulation that facilitates the transdermal delivery of BoNT. The formulation was homogeneous, stable, and efficacious. In a mouse model, we evaluated the neurotoxin’s impact on neuromuscular function using the Digital Abduction Score (DAS) for toe-spread and rota-rod assay to assess motor coordination. Results: The results confirmed the successful paralytic effect of the neuotoxin. The formulation significantly reduced sweating in the hyperhidrosis mouse model, indicating the therapeutic potential for this indication. Beyond the neurotoxin’s paralyzing effect, we also observed the recovery of nerve function, showing that the neurotoxin does not cause permanent damage, further underscoring its safety and efficacy. Conclusions: This formulation is the first of its kind to successfully deliver a large biomolecule like BoNT across the skin and produce a therapeutic effect. The ability to deliver large biomolecules transdermally has the potential to serve as a platform technology for treating a variety of conditions, including neuromuscular disorders, skin conditions, and localized pain management. Full article

Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin^®; 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX^®; 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (CMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC₅₀, ID₅₀, and ED₅₀ values (pooled mean ± SEM), was displayed by incobotA compared to onabotA in the CBPA (EC₅₀: incobotA 7.6 ± 0.7 U/mL; onabotA 5.9 ± 0.5 U/mL), CMAP (ID₅₀: incobotA 0.078 ± 0.005 U/rat; onabotA 0.053 ± 0.004 U/rat), and DAS (ED₅₀: incobotA 14.2 ± 0.5 U/kg; onabotA 8.7 ± 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products. Full article