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Botulinum Type A: Key Clinical Postulates


Botulinum type A injections are widely used across the dermatology and aesthetic medicine specialties. At the Fall Clinical Dermatology Conference 2021, Mark S Nestor, MD, PhD, highlights how to optimize the neurotoxin to improve patient care.

While botulinum type A acts identically and can come in commercial multiple forms, how does it compare with regards to clinical aspects?

Mark S. Nestor, MD, PhD, dermatologist and executive director of aesthetics at the Hair and Regenerative Medicine (FRED), Director for Center for Cosmetic Enhancement and the Center for Clinical and Cosmetic Research, Aventura, Florida, and voluntary professor at the Department of Dermatology and Cutaneous Surgery Department of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, Florida, dove into that question at Fall Clinical Dermatology Conference 2021, held October 21-24 in Las Vegas, Nevada.1

Nestor emphasized that understanding the clinical science of botulinum type A will help optimize patient care.

Nestor explained 8 postulates about botulinum type A:2,3

Postulate 1: All Type A toxins act identically.

  • Associate proteins dissociate quickly in the syringe, and do not play a role in the binding or activity of the 150 kilodalton (kDa).
  • Recovery after the procedure is the least understood part of the treatment process, Nestor said, and there may be a genetic factor causing the differences.

Postulate 2: The efficacy of treatment is based on the equation between toxin and receptor. The clinical efficacy is influenced by molecular potency and patient attributes including muscle mass, gender, age, and ethnicity.

  • The rate of efficacy is limited by the binding of the H chain to receptors at the presynaptic surface.
  • The clinical effect factors include molecular potency, patient characteristics, and toxin distribution.

Postulate 3: The efficacy, onset, and duration of treatment are all functions of molecular potency.

  • Molecular potency is defined as the number of active 150 kDa molecules available for binding.

Postulate 4: The molecular potency is hard to objectively quantify.

  • The unit of measure for each toxin is different for each manufacturer and measured by different tests, this prevents direct comparisons of botulinum type A, and there may be differences on 150 kD amount, availability, or activity.
  • The methods of comparisons for molecular potency include independent trial data, different toxins for different patients in a single trial (non-inferiority), bilateral comparison of different toxins in a single patient, and direct measurement of toxin and activity.
  • When comparing independent trial data there are different protocols, scales, and investigators, meaning it is not always accurate or reliable.
  • When using a non-inferiority trial for comparison, a comparison can be made with a glabellar line result.
  • Multiple studies have been done by Nestor in using bilateral comparison of different toxins in a single subject.4-6

In the double-blinded Frontalis Trial,4 22 female patients (ages 19-63) were treated for severe frontalis rhytids at maximum elevation with either 5 units of AbobotulinumtoxinA (ABO) (Dysport; Ipsen Biopharmaceuticals) or 2 units of OnabotulinumtoxinA (ONA) (Botox; Allergan) at 5 contralateral sites. The units were identical volumes of 0.04 ml: Diluted with 2.4 ml of non-preserved saline (NS) per 300 units of ABO and 2.0 ml of NS per 100 units of ONA: a 2.5:1 unit ratio, according to Nestor.

It was found that the overall median onset of ABO was 1.8 days and ONA was 3.8 days with the duration of the procedure lasting a median of 104 days vs 84 days, respectively.

Postulate 5: The increased molecular potency, to a certain point, will decrease the time to onset and increase duration of effect. Nestor broke this down to molecular potency quotient (MPQ) as the amount of molecular potency units divided by the cost. MPQ and molecular potency of ABO was examined in a clinical trial, Nestor explained, which found that the data was consistent with molecular potency showing early onset and long duration at comparable dosing (high MPQ).7

Postulate 6: Toxin diffusion is a misnomer and toxin spread—physical movement of toxin from the original injection site—is dependent on the technique.

  • Nestor said the molecular potency (as well as diffusion and spread) of the toxin will change the area that is affected.
  • The most important factor when it comes to the procedure is the area of clinical effect, according to Nestor, which is the spread of the toxin suspension multiplied by the molecular potency. The lower the molecular potency, the smaller the area that is affected.

Postulate 7: Optimal reconstitution volume can improve distribution and can then improve onset, efficacy, and duration of effect. Nestor showed that multiple factors can impact the treatment such as the various standard methods for each botulinum toxin type A, off-label volumes vary from 1 to 5 units, and volumes that are too small or too large can widely change the effect of the toxin.

Postulate 8: An increased number of injection sites can optimize toxin distribution and improve onset, efficacy, and duration of effect.

Nestor concluded his presentation with the notion that fully understanding the clinical science of botulinum toxin type A will help physicians compare the toxins available whileoptimizing patient care.


  1. Nestor, MS. The science of botulinum toxin type A: key clinical postulates. Presented at: Fall Clinicals Dermatology Conference 2021; October 21-24; Las Vegas, Nevada, and virtually.
  2. Nestor MS, Kleinfelder RE, Pickett A. The use of botulinum neurotoxin type a in aesthetics: key clinical postulates. Dermatol Surg. 2017;43 Suppl 3:S344-S362. doi:10.1097/DSS.0000000000001412
  3. Nestor MS, Arnold D, Fischer D. The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II. Journal of Cosmetic Dermatology. 2020;19(11):2785-2804. doi:10.1111/jocd.13702
  4. Nestor MS, Ablon GR. The Frontalis Activity Measurement Standard: a novel contralateral method for assessing botulinum neurotoxin type-A activity. J Drugs Dermatol. 2011;10(9):968-972.
  5. Nestor, M.S., Ablon, G.R. Comparing clinical attributes of AbobotulinumtoxinA and OnabotulinumtoxinA utilizing a novel contralateral frontalis model and the frontalis activity measurement standard. J Drugs Dermatol. 10(10):1048-1057, 2011.
  6. Nestor, M.S., Ablon, G.R. Duration of action of AbobotulinumtoxinA and OnabotulinumtoxinA: a randomized, double-blind, study using a contralateral frontalis model. J Clin Aesthet Dermatol. 4(9):43–49, 2011.
  7. Nestor M, Cohen JL, Landau M, et al. Onset and duration of abobotulinumtoxina for aesthetic use in the upper face: a systematic literature review. J Clin Aesthet Dermatol. 2020;13(12):E56-E83.


Nestor is a consultant for Aerolase, Croma Pharma GmbH, DermTech, Fastox Pharma, Ferndale, Ipsen Biopharmaceuticals, Kimera, Kyrstal Biotech, Mediwound, Novaestiq Corp, Plasmend, Pulse Biosciences, Revian, Rohrer Aesthetics, Seaspire, Sensus Healthcare, Sirnaomics, and Suneva Medical.

He has received research grants from Arcutis Biotherapeutics, Biofrontera, Bioregenerative Aesthetics, Inc., BirchBioMed, Brickell Biotech, Croma Pharma GmbH, DermTech, DUSA Pharmaceuticals, Eirion Therapeutics, Ferndale, Galderma, Krystal Biotech, Mediwound, Merz Pharma, miRagen Therapeutics, Plasmend, Pulse Biosciences, Sirnaomics, SkinJect, Inc, and Sueva Medical.

He is on the advisory board for Allergan, Biofrontera, BirchBioMed, Castle Biosciences, Eirion Therapeutics, Fastox Pharma, Ferndale, Galderma, Novaestiq Corp, Sensus Healthcare, and Sirnaomics. He is a speaker for Sensus Healthcare and a shareholder of Strathspey.

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