AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

Abstract

Botulinum neurotoxin type-A (BoNT-A) blocks the release of acetylcholine from peripheral cholinergic nerve terminals and is an important option for the treatment of disorders characterised by excessive cholinergic neuronal activity. Several BoNT-A products are currently marketed, each with unique manufacturing processes, excipients, formulation, and non-interchangeable potency units. Nevertheless, the effects of all the products are mediated by the 150 kDa BoNT-A neurotoxin. We assessed the quantity and light chain (LC) activity of BoNT-A in three commercial BoNT-A products (Dysport®; Botox®; Xeomin®). We quantified 150 kDa BoNT-A by sandwich ELISA and assessed LC activity by EndoPep assay. In both assays, we assessed the results for the commercial products against recombinant 150 kDa BoNT-A. The mean 150 kDa BoNT-A content per vial measured by ELISA was 2.69 ng/500 U vial Dysport®, 0.90 ng/100 U vial Botox®, and 0.40 ng/100 U vial Xeomin®. To present clinically relevant results, we calculated the 150 kDa BoNT-A/US Food and Drug Administration (FDA)-approved dose in adult upper limb spasticity: 5.38 ng Dysport® (1000 U; 2 × 500 U vials), 3.60 ng Botox® (400 U; 4 × 100 U vials), and 1.61 ng Xeomin® (400 U; 4 × 100 U vials). EndoPep assay showed similar LC activity among BoNT-A products. Thus, greater amounts of active neurotoxin are injected with Dysport®, at FDA-approved doses, than with other products. This fact might explain the long duration of action reported across multiple indications, which benefits patients, caregivers, clinicians, and healthcare systems.

Duration of Symptom Relief Between Injections for AbobotulinumtoxinA (Dysport®) in Spastic Paresis and Cervical Dystonia: Comparison of Evidence From Clinical Studies

“…In the research of Field et al, the ELISA assay was used to quantify the amount of 150-kDa BoNTA protein per unit (and per vial) of each product, and the EndoPep assay was used to quantify the catalytic light chain activity of BoNTA in the different products (specifically, its ability to cleave the SNAP-25 protein, which is how it exerts its effect on muscular activity). The results showed that there was no FIGURE 6 | Quantity of active 150-kDa BoNTA in BoNTA products at their total recommended doses (22). The total recommended doses shown are for France.…”

Botulinum Toxin and Neuronal Regeneration after Traumatic Injury of Central and Peripheral Nervous System

“…For completeness it must be remembered that Luvisetto et al [57] and Marinelli et al [59] injected a relatively high concentration of toxin, namely 15 pg/paw in CD1 mice weighing 35-40 g, compared to doses that induce analgesic effects in mice in other pain models [40], or as measured in other reports investigating BoNT/A toxicity [60,61]. However, in the cited reports [57,59], the authors reported no side effects in their experiments and the concentration used was considered safe.…”

The whole truth about botulinum toxin – a review

“…They are associated with systemic and generalized botulinum toxin diffusion. There are two classes of adverse events reported so far -transient and benign events, and potentially serious events [1][2][3][4][5][6]. It seems to be important to gain appropriate knowledge about all possible adverse effects, their mechanisms and ways of preventing them.…”