5 Basic science
Abobotulinum toxin A
Summary and Key Features
• Abobotulinum toxin is a botulinum toxin-A with very similar features to the other type A botulinum toxins
• The accessory proteins that surround the neurotoxin protein are already dissociated in the vial
• Is ‘diffusion’ an issue? Clinical studies supporting both issues are presented
• Equivalency between abo- and obobotulinum toxins is approximately 2.5; a true number is impossible to define as the units – Speywood units versus Botox units – are measured differently
• Because the clinical products Dysport® and Azzalure® are identical, except for the number of Speywood units per vial, all clinical data for one product can be considered applicable to the other
• Clinical trials in the United States and Europe confirm both efficacy and safety for glabellar injection for frown lines
• Other features evaluated include time of onset, efficacy, and safety with re-injection and dose equivalency to glabellar muscle mass
• Reviews of the international consensus board for dosage and treatment technique gave recommendations for injections at both upper and lower facial sites
• Parameters for safe injections with abobotulinum toxin are reviewed
• Dosage and dilution are important determinant points for efficacy, duration, and field of effect.
Before the BoNT-A neuroprotein can become active, the NAPS must release the active BoNT-A 150 kDa neuroprotein from the progenitor complex. This occurs with a change in environment to a physiological pH. The issue arises as to when this occurs. Earlier pilot in vitro studies by Eisele & Taylor showed the timescale of release varied from immediate with pH change to a delay from minutes to hours, depending on the product serotype with BoNT type B taking longest. A recent study by Merz Pharmaceuticals, reported by Eisele et al in 2011, found that the naked neuroprotein was released from its associated complex in less than 1 minute with a change to physiological pH; this occurs with both onabotA and abobotA. The investigation implied that release of the naked neuroprotein probably occurs in the vial during reconstitution, well before injection and tissue spread. However, definitive studies on complex dissociation by the same group were also published in 2011 and clearly demonstrated that all the BoNT type A products existed as free neurotoxin within the vials even before reconstitution. In other words, the manufacturing processes for the products all released the free BoNT neurotoxin during manufacture.
These biochemical studies do have implications for clinical usage in understanding efficacy and safety of each product. With the neurotoxin protein of 150 kDa released before injection, the active toxins are stoichiometrically similar and one would not expect a difference in diffusion since complex size is now shown to be irrelevant. It is the authors’ opinion that the difference seen with the products has to do with dosage-unit differences and volume reconstitution. The relative kinetics of dissociation versus diffusion have implications for the safety profiles of the various formulations of BoNT-A in current or future clinical use, and therefore these remain contentious issues for their respective manufacturers, as reported by Pickett in 2009.