The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II

Abstract

Background: The literature on botulinum neurotoxin type A (BoNT-A) is extensive, often contradictory, and confounded by a competitive market of products and research attempting to distinguish brand individuality.

Methods: A comprehensive review of literature on the principles of BoNT-A in aesthetics as well as clinical examples.

Results: In 2017, the Eight Key Clinical Postulates were formulated as a guide for the aesthetic practitioner in understanding BoNT-A pharmacodynamics and to compare different toxins. These are now updated to include (a) All type A toxins act identically; (b) The mathematical relationship between toxin and receptor is the basis of efficacy, and clinical efficacy is influenced by molecular potency and patient attributes including muscle mass, gender, age, and ethnicity; (c) Efficacy, onset, and duration are functions of "molecular potency" defined as the number of active 150 kDa molecules available for binding; (d) "Molecular potency" is difficult to objectively quantify for commercially available toxins; (e) Up to a point, increased molecular potency decreases time to onset and increases duration of effect, and the "Molecular Potency Quotient" is a construct for comparing molecular potency commercial cost; (f) The area of effect of a toxin injection is dependent upon molecular potency, diffusion (passive), and spread (active); (g) Differing reconstitution volumes; and (h) Increased number of injection sites can affect spread, onset, and duration of effect.

Conclusions: The principles of BoNT-A use in aesthetics are complex yet understandable as outlined in the framework of the updated Eight Key Clinical Postulates and serves as a useful tool for providing the most effective treatment and interpreting research on present and future toxin formulations.

Keywords: BoNT-A; botulinum neurotoxin type A; key clinical postulates; molecular potency; review.

FIGURE 1

Ligand‐receptor–binding model for toxin and its corresponding receptor. Bulk botulinum toxin is complexed with neurotoxin‐associated complexing Proteins and formulated with human serum albumin in the vial before becoming free type A neurotoxin (150 kDa) in a neutral to basic environment, such as upon reconstitution. Following injection, the complex‐free neurotoxin binds to 2 extraneuronal receptors, allowing bound neurotoxin to undergo endocytosis. The translocated neurotoxin is able to move intracellularly across the neuronal cytosol to the intracellular target, SNAP‐25, inducing proteolysis. Proteolysis of SNAP‐25 induces blockade of acetylcholine release into the postsynaptic neuromuscular junction, resulting in muscular paralysis. (Adapted from Simpson ⁶² and Lebeda et al ¹⁴⁸ )

FIGURE 2

Percentage of subjects exhibiting partial efficacy from AbobotulinumtoxinA/OnabotulinumtoxinA at various time points. ⁴⁴ ABO, abobotulinumtoxinA; FMS, Frontalis activity Measurement Standard; ONA, onabotulinumtoxinA

FIGURE 3

Measurement of frontalis height and wrinkle severity using the Frontalis activity Measurement Standard at baseline (left image) and 2 d following injection (right image). AbobotulinumtoxinA was injected into the patient's left frontalis (right side of images). OnabotulinumtoxinA was injected into the right frontalis (left side of image) ⁵⁵

FIGURE 4

Formula for molecular potency quotient

FIGURE 5

Like toxin, sugar always disperses uniformly when poured onto a flat surface given that all external variables are conserved meaning that diffusion and spread are equal. As demonstrated in the above image, a larger number of molecules of sugar akin to increased molecular potency of toxin administered (left) will yield a greater area of effect than a smaller quantity of the same “toxin” administered (right)

FIGURE 6

Formula for calculating area of effect

FIGURE 7

If diffusion and spread are equal, the difference in area of effect is due to molecular potency ¹⁰⁵

FIGURE 8

Difference in area of effect due to differing reconstitution volumes; 1.5cc (small blue circle) versus 2.5cc (large blue circle); baseline on the left, day 14 on the right ¹¹⁶

FIGURE 9

Difference in area of effect of 2 injection points versus 5 injection points ¹¹⁶

FIGURE 10

Difference in frontalis muscle elevation and longevity with 2 injection points versus 5 injection points of AbobotulinumtoxinA. Five‐point injection shows less mm of movement and thus greater efficacy at each time point vs. 2‐point injection ⁸