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Basic science: Myobloc®


Summary and key features

  • BTXB is believed to have an increased radius of diffusion when compared with BTXA

  • Rate of onset of BTXB is increased over BTXA

  • Although dose-dependent, the duration of BTXB effect has not been shown to be equivalent or longer than that of the type A toxins.

  • Most cosmetic dermatologists use a ratio of 1 U of BTXA to 50 U of BTXB

  • BTXB injections are related with increased pain and burning sensation compared with BTXA.

The use of botulinum toxins for the improvement of fine lines and facial wrinkles has become increasingly popular over the past several years. By utilizing toxins to target hyperfunctional facial rhytids, physicians are able to successfully treat aging skin, yielding aesthetically younger, smoother looking skin to patients. The occurrence of glabellar lines is due to the constant pulling of the skin by the musculature below. Active muscle movement of the transverse head of the corrugator supercilii results in the vertical glabellar lines, while the oblique head of the corrugator supercilii and the depressor supercilii along with the orbicularis oculi muscles contribute to the formation of the oblique glabellar line. The approach to treatment includes minimizing the appearance of the glabellar lines by considering options of microdermabrasion, chemical peel, injections of collagen, silicone, autologous fat or dermis, or plytera fluoroethylene. There are also surgical venues of endoscopy or limited incision to modify function of the corrugator supercilii and procerus muscle and direct incision of the glabellar line.

In 1992, Carruthers et al. evaluated the use of Clostridium botulinum type A purified neurotoxin complex (BTX-A; Botox, Allergan Inc., Irvine, CA) to eradicate glabellar rhytids by chemically denervating the corrugator supercilii. Findings included that botulinum toxin blocked the release of acetylcholine from motor nerve endings, resulting in a decrease in muscle tone and over-activity that was dose dependent. It was also noted that botulinum toxin provided a safe treatment that targeted the muscle activity that contributed to the formation of wrinkle lines. Since then, myriad of other studies have yielded similar results, and the BTX-A is currently FDA-cleared for use in moderate to severe glabellar lines.

Botulinum toxin type B (BTX-B; Myobloc in the USA and Neurobloc in Europe; otherwise identified as Myobloc henceforth, Solstice Neurosciences, South San Francisco, CA) was FDA-cleared in 2000 for the treatment of abnormal head position and pain related to cervical dystonia. Currently its clinical utility is being investigated for a variety of other medical disorders, such as hyperhidrosis and sialorrhea, as well as in the setting of cosmetic dermatology. It is readily available in a liquid formulation which requires no preparation or reconstitution unlike BTX-A.

Pharmacology of botulinum toxin B

The molecular weight of the BTX-A complex is around 900 kDa, whereas that of Myobloc is approximately 700 kDa. Both these complexes are found to be stable in acidic conditions. The large neurotoxin complex is composed of proteins such as a hemagglutinin and a non-toxic, non-hemagglutinin moiety. The active neurotoxin is a 150 kDa dimer consisting of heavy chain (100 kDa) and a light chain (50 kDa) moiety linked together by a disulfide bond.

The mechanism of action of Botulinum toxin B on the nervous system is similar to that of all other botulinum toxins that involves a series of cellular actions including binding, internalization, and inhibition of acetylcholine release. The heavy chain contributes to the irreversible binding of the toxin to the serotype-specific protein within the soluble N -ethyl maleimide-sensitive factor attachment protein receptor (SNARE) complex, which is involved in release of acetylcholine-containing vesicles from the presynaptic neuron. Flaccid paralysis associated with botulism is due to the light chain-mediated proteolysis of SNARE proteins and the subsequent inhibition of synaptic vesicle fusion to the presynaptic membrane of the human motor neurons Tis. Each serotype cleaves a specific residue on one of the N -ethyl maleimide-sensitive factor attachment proteins ( Table 7.1 ). Myobloc cleaves vesicle associated membrane protein (VAMP) also known as synaptobrevin. Serotypes F, G, D also cleave VAMP, but at various locations. It is found that the various sites of action of various serotypes may contribute to the differences in clinical effectiveness. SNARE proteins may be the only intracellular targets of BTX serotypes. The remarkable specificity of the BTX light chain cleavage is due to the light chain recognizing unusually long SNARE sequences (∼30 to 50 residues indicated by the specific serotype) .

TABLE 7.1
Pharmacology of Botulinum Toxins Botulinum Toxin Serotypes by Target/Cleavage Sizes
Adapted from Jankovic et al.
Serotype Target Size Cleaves At
A SNAP-25 a Gln197–Arg198
B VAMP b Glu76–Phe77
C Syntaxin Lys253–Ala254
Lys252–Ala252
SNAP-25 a Arg198–Ala199
D VAMP b Ala67–Asp68
Lys59–Leu60
E SNAP-25 a Arg180–Ile181
F VAMP b Gln58–Lys59
G VAMP b Ala81–Ala82

a SNAP-25 is soluble NSF attachment protein of 25,000 kDa.

b VAMP is vesicle-associated membrane protein (synaptobrevin).

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