Botulinum toxin is a naturally occurring neurotoxic protein produced by the bacterium Clostridium botulinum. It is used to treat conditions ranging from muscular spasm to migraines to wrinkles. In 2002, the US Food and Drug Administration (FDA) approved botulinum toxin type A for the treatment of moderate to severe glabellar furrows, and it has since been used routinely by dermatologists "off label" for total facial and neck rejuvenation. Botulinum toxin has 7 distinct serologic types lettered A to G; the most common type used in the US is type A. Until recently the only botulinum toxin A approved by the FDA and available in the United States was Botox® (Allergan, Irvine, California). Dysport (Medicis, Scottsdale, Arizona.), which has been available in 65 other countries is now the second botulinum toxin A to be approved for use in the US and will be available as of July 2009. Botulinum toxin type B, available under the trade name Myobloc® (Solstice Neurosciences, Malvern, Pennsylvania), is approved for treating cervical dystonia. Two additional type A toxins are in US clinical trials: Xeomin® (Merz Pharmaceuticals, Greensboro, North Carolina), and PurTox® (Mentor Corporation, Santa Barbara, California).

There are differences among these type A neurotoxins. Botulinum toxin type A in its innate form is a 150-kDa protein composed of both a heavy and a light chain. This "naked" protein is surrounded by a hemagglutinin protein complex. ( like a jacket or coat). The only purpose of this complex is to protect the naked protein from degradation by stomach acid (and may be irrelevant for injectable botulinum toxin). At some point during or after injection at a physiologic pH, the hemagglutinin proteins dissociate, leaving the same 150-kDa protein regardless of the product. The heavy chain then allows for attachment of the toxin to the axon terminals, and the light chain degrades synaptosome-associated protein 25 kDa, a protein that is required for signal transduction. Both PurTox® and Xeomin® are "naked" toxins without surrounding hemagglutinin proteins. The current thinking is that when patients develop antibodies to neurotoxins, it is to the surrounding proteins and not to the toxin itself. These injectable neurotoxins also contain human serum albumin in the vial, and, depending on the brand, sucrose or lactulose as stabilizers.

Dysport®

Currently approved in over 65 other countries (Reloxin® was to be the new name in the US but it will retain its current moniker). Dysport® is a type A botulinum toxin that was approved by the FDA for the improvement of lines in the glabellar complex. Whereas Botox® is purified by repeated precipitation and redissolution, Dysport® is manufactured by using a column separation method. These distinct purification processes produce differences in the multihemagglutinin protein complex that surrounds the neurotoxin. (ie: "the coats" ) Whether the difference in this complex is important is unclear, but clinical trials to date have shown differences in the onset of action and duration of Dysport® compared with Botox®.

Dosage differs between Botox® and Dysport®. In addition to dose and onset of action, another distinguishing factor of Dysport® is its field of effect. Studies suggest that a broader softening is achieved with Dysport® than with Botox®. Findings indicate that the neurotoxin not only relaxes the muscle groups into which it is injected but also has a varying level of adhesion and retention into surrounding muscle groups, which produces an overall softening effect. The demarcation between injected and noninjected areas may not be as apparent with Dysport®. This may be an advantage in areas such as the neck or forehead but may be less optimal in areas where diffusion is not wanted such as near the eyebrows. A study using 2.5:1.0 Dysport:Botox dose ratio, Botox was more effective for wrinkle treatment. In a previous trial, a 4:1 ratio produced equivalent efficacy, but the patients receiving Dysport had a significantly higher risk for adverse effects. This suggests that the optimal conversion ratio will be somewhere in between. Clearly, proper use of Dysport will involve a learning curve once available in the US.

PurTox®

PurTox® is a type A neurotoxin that is currently in phase 3 testing for glabellar lines as well as therapeutic indications. Compared with the other botulinum toxin type A products, PurTox® has a higher concentration of human serum albumin and, like Xeomin® , is a "naked" toxin without surrounding hemagglutinin proteins. ( no coat for purtox!) . In phase 3a studies, 400 patients had 30 units injected into the glabellar complex; onset of action was noted at day 3 and follow-up extended to 180 days.

Xeomin®

Xeomin®, like PurTox®, is an uncomplexed (naked--no coat) botulinum toxin A product. It is approved for treating blepharospasm and cervical dystonia in Europe, Mexico, and Argentina. It is also indicated for the cosmetic treatment of glabellar frown lines in Argentina, and is beginning phase 3 trials in the United States. Initial results showed Xeomin® is almost identical to that for Botox®. The average duration of Xeomin® was 3.7 months, compared with 3.5 months for Botox®. In terms of potency, Xeomin® appears to exhibit a 1:1 dose ratio compared with Botox® , and there was also no apparent difference in field of effect between these two. For therapeutic uses, safety and efficacy did not significantly differ. However, the lack of protein coat may decrease the chance of developing antibodies and subsequent tolerance to this drug with high doses needed for some therapuetic indications, or possibly long term use for cosmetic purposes.