Session Title: AA 2021 Virtual Posters - Neurological Rehabilitation
Session Time: None. Available on demand.
Disclosures: David Rupp, BS: No financial relationships or conflicts of interest
Objective: Unit potencies of botulinum neurotoxin type A (BoNT/A) drugs are not interchangeable due in part to unique manufacturing processes and drug formulations. Various excipients are used to stabilize BoNT/A and prevent adsorption to surfaces. We evaluated the effect of a cell-penetrating peptide (CPP) in a prototype formulation to determine if it could stabilize BoNT/A against adsorption and thermal aggregation and contribute to a longer duration of action.
Design: A CPP with the sequence RKKRRQRRRG-[K]15-GRKKRRQRRR was synthesized and tested for its effects on BoNT/A using toxin adsorption, in vivo potency, and duration analyses.Setting : Not applicable.Participants : Not applicable.
Interventions: Not applicable.
Main Outcome Measures: Size-exclusion high-performance liquid chromatography compared adsorption of 150-kDa BoNT/A toxin formulated in either potassium phosphate/NaCl buffer containing polysorbate 20 (PS20), CPP with and without PS20, human serum albumin (HSA), or in buffer alone. Mouse digit abduction score (DAS) testing compared the potency and duration of 150-kDa BoNT/A toxin at an approximate ED50 dose formulated in histidine buffer/trehalose buffer containing PS20, CPP/unit BoNT/A with or without PS20, or in bovine serum albumin (BSA)/NaCl.
Results: Toxin adsorption to the glass surface occurred in buffer control and CPP-only solutions at 7 hours, both with toxin recovery of < 64%. At 14 and 21 hours, buffer control and CPP-alone samples had decreased toxin recoveries of < 42%; samples containing HSA or PS20 continued to display toxin recoveries of >95%. In the DAS assay, BoNT/A prepared in polysorbate formulations with or without CPP exhibited similar, predictive DAS efficacy (>ED50) and duration versus formulation in BSA/NaCl. In contrast, the formulation in CPP alone, without PS20, demonstrated decreased potency (Conclusions: Inclusion of a CPP in a BoNT/A formulation neither prevents toxin adsorption nor increases potency or duration.
Level of Evidence: Level II
To cite this abstract in AMA style:Rupp D, Nicholson G, Briode RS, Nino CR, Do M, Wan J, Vazquez-Cintron E, Wu C, Brin M, Brideau-Andersen A. A Cell-penetrating Peptide (CPP) Did Not Decrease 150-kda Bont/a Toxin Adsorption to Surfaces or Increase Toxin Potency or Duration in a Prototype Formulation [abstract]. PM R. 2021; 13(S1)(suppl 1). https://pmrjabstracts.org/abstract/a-cell-penetrating-peptide-cpp-did-not-decrease-150-kda-bont-a-toxin-adsorption-to-surfaces-or-increase-toxin-potency-or-duration-in-a-prototype-formulation/. Accessed December 9, 2023.
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PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/a-cell-penetrating-peptide-cpp-did-not-decrease-150-kda-bont-a-toxin-adsorption-to-surfaces-or-increase-toxin-potency-or-duration-in-a-prototype-formulation/