Botulinum Toxin Type A

New Information About an Old Medicine

Kevin C. Smith, MD, FRCPC (Dermatology)

Disclosures

Skin Therapy Letter. 2011;16(8) 

In This Article

Widening Applications

Since Alan Scott's pioneering use of BoNT-A for the treatment of blepharospasm and strabismus, various formulations of this versatile biological product have been reported to be useful in the management of over 140 medical, surgical, and aesthetic indications. Of interest to dermatologists, indications that regulatory authorities have approved for marketing and advertising in Canada include (for onabotulinumtoxinA) treatment of upper facial rhytides, including forehead, lateral canthus and glabellar lines,[10] as well as for the treatment of hyperhidrosis of the axillae in patients 18 years of age and older.[10] It is expected that other formulations of BoNT-A could receive similar regulatory approval for marketing and advertising in Canada in the future.

When they were first introduced, medicines incorporating BoNT-A were used to block the vesicle-mediated release of the neurotransmitter acetylcholine, and so produce for a period of several months very precise and localized relaxation of the striated muscles to which it was applied by injection.

The first suggestion that BoNT-A could be used for purposes other than muscle relaxation came from Bushara and Park in 1994, who observed reduced sweating in the treated area when BoNT-A was used for treatment of hemifacial spasm.[11] Based on observations that BoNT-A was useful for controlling excessive sweating, it was found to also be beneficial for the control of persistent facial flushing,[12] gustatory sweating (Frey's syndrome),[13] and for conditions made worse by excessive sweating and associated maceration (e.g., familial benign pemphigus (Hailey-Hailey disease),[14] dishydrotic eczema,[15] and inverse psoriasis[16]). Its use was even extended to the treatment of facial chromhidrosis[17] where part of its mechanism of action was thought to come from inhibition of the release of substance-P.[18] Excessive lacrimation,[19,20] chronic rhinitis,[21,22] sialorrhea,[23] and parotid fistulas resulting from skin cancer surgery[24,25] have also been reported to respond to treatment with BoNT-A.

Basic science research has shown that BoNT-A blocks the vesiclemediated release of neurotransmitters other than acetylcholine, including substance-P,[26] glutamate,[27] and calcitonin-gene related peptide.[28] These properties of BoNT-A may account for its neuromodulating effect on autonomic nerves,[29] which makes possible the use of BoNT-A as a therapeutic option for Raynaud's phenomenon, where treatment with BoNT-A can be safer and simpler than sympathectomy. Onset of action occurs within days and lasts for months, controlling rest pain, shortening and reducing the severity and frequency of attacks, and speeding the healing of ischemic ulcerations.[30–33]

The observation that BoNT-A inhibits the release of some painmediating neurotransmitters, such as substance-P, helps to explain why BoNT-A has proven useful in the management of a variety of painful conditions, including headache,[34–36] multiple cutaneous piloleiomyomas,[37] notalgia paresthetica,[38] and postherpetic neuralgia in the trigeminal distribution, but not on the trunk or extremities.[33]

BoNT-A has even proven to be of value in athletes, for example as a treatment for an intention tremor known as "the yips," afflicting up to 30% of golfers.[39] Similar dystonias and occupational cramps that can occasionally trouble dermatologic surgeons might also benefit from treatment with BoNT-A.

Systems for the topical administration of BoNT-A are in development,[40,41] and may turn out to be useful for certain medical and aesthetic indications.

The N-terminal light chain component of BoNT-A (known as LC) is the part that cleaves SNAP-25, resulting in the blockade of vesicle-mediated release of a variety of neurotransmitters. This component (or the corresponding LC element from other botulinum neurotoxins) can be attached to a variety of ligands, which are proteins that bind to various glycoproteins that are specific for certain cell types or can be produced by recombinant techniques.[42,43]

It is likely that such derivatives of BoNT-A and other clostridial neurotoxins, which are now emerging from the labs and in some cases entering clinical trials, will become commercially available. These advances are poised to extend the utility of this class of medications to tissues that are currently unresponsive to BoNT-A, improve tissue specificity, modulate durations of action, and benefit our patients in ways that remain to be explored.

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