Botulinum Toxin 2012: Where are we now? Part 1

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Joel Cohen, MD

In this presentation, Dr Cohen reviews the use of botulinum toxins in clinical practice. He reviews the three Type A toxins such as Botox, Dysport, and Xeomin.

Science and Data To Be Considered

It is important that clinicians understand the molecular structure of Botulinum neurotoxin type A.



The core neurotoxin protein in all agents used clinically is 150kD BoNT/A.  Botox and Dysport both have accessory proteins that surround the core neurotoxin, while Xeomin lacks accessory proteins.

Botulinum toxin Type A works via chemodenervation, in that the internalized toxin binds to the SNAP-25 target protein and then blocks the exocytosis of acetylcholine into the synaptic cleft following a neural impulse.  This effectively denervates the segment of muscle supplied by the affected cholinergic nerve terminal.

Differentiating Botulinum Toxins

Regulatory agencies worldwide have recognized that these products are not interchangeable. The units of biologic activity in each available product cannot be compared or converted into the units of any of the other available products, nor can the doses or preparations be interchanged.

Immunogenicity

Dermatologists should be aware that botulinum toxin itself could be immunogenic. The protein added to stabilize the product also has immunogenic properties. If antibodies occur, the question is whether or not they are neutralizing “critical domain” antibodies or non-neutralizing “non-critical domain” antibodies.  Antibody detection can measured through two tests. The Mouse Protection assay is the most widely used with the highest specificity. The patient’s serum is taken and given to a mouse. The mice are then given a lethal dose of BTX-A. If the mouse lives, the patient has antibody; in most cases the mouse would die. The rapid immunoassays (ELISA, W. BLOT) have a lower specificity and a lack of correlation between detected abs and clinical resistance.

Various data and studies suggest that overall, few patients may develop antibodies; however, they if they do develop antibody, they seem to continue to respond to the products.