Wednesday, January 6, 2010

Neurotoxins: Dysport and Botox

Medscape has a nice CME article on neurotoxins, Dysport® and Botox® Cosmetic. Dysport is abobotulinumtoxinA. Botox Cosmetic is onabotulinumtoxinA. Dr Monheit begins with the interesting history of botulinum toxin.

1895: Clostridium bacterium identified

1940s: BoNT-A purified (Schantz and colleagues)

1950s: BoNT-A mechanism of action elucidated

1970s: BoNT-A investigated as a treatment for strabismus (Dr. Alan B. Scott)

1979 Botulinum neurotoxin type A was approved by the FDA [US Food and Drug Administration] and became a registered mechanism for use in ophthalmology. It was called Oculinum at first.

1987: Dr. Jean Carruthers notices effect on the glabella when treating patients with BoNT-A for blepharospasm.

1989: Botox approved by FDA for the treatment fo strabismus and blepharospasm (originally approved under the brand name Oculinum)

1992: Dr. Jean Carruthers and Dr. Alastair Carruthers publish seminal paper on the use of BoNT-A for the aesthetic treatment of glabellar rhytides.

2002: Botox Cosmetic approved by FDA for the treatment of glabellar rhytides.

2009: Dysport approved by FDA for the treatment of glabellar rhytides.

Dr. Monheit then procedes to describe the science beginning with the molecule itself and the subtypes. He points out that the active neurotoxin protein at 150 kD is the same for both Botox and Dysport. It is the surround complex that is different. (photo credit)

We have in the botulinum toxin molecule a heavy chain (100 kD) and a light chain (50 kD). It's actually the light chain that is responsible for the nicking and the final cleavage that occurs.

Upon absorption into the body, the complex disassociates, and we're left with the bare neurotoxin molecule.

As we understand the science and the technical variables, such as the neurotoxin protein at 150 kD, the hemagglutinin and nonhemagglutinin proteins, the difference in the complex sizes -- 300 kD and 900 kD (depending on whether we're talking about the Botox® molecule or the Dysport® molecule)..

Dr. Monheit proceeds to go through the clinical trials and tips/cautions for proper use of the neurotoxins. You can either listen to his lecture or read the transcript. I found it to be an enjoyable lecture.

The central difference between Dysport® and Botox® Cosmetic is the dosage units. The units of measurement for the 2 botulinum neurotoxin A products are proprietary measures that are different for each product. The injection points for the 2 products do not differ significantly, and the toxin molecules have the same molecular weight. Differences in onset of action have not been demonstrated in clinical trials.

One of the important things for you to feel comfortable with is the dilution [you] can [or] should use. As you know, as you add more saline, or dilute it more, you do get more spread. You also have more volume that you're putting in. The dilution used for all of the clinical studies was 1.5 mL. Many people are comfortable with 2.5 mL. In Europe, they're using either 2.5 or 1.5 mL, giving the number of units you see in both Botox® and Dysport® [units]. But rather than try to translate these units back and forth, you should learn to live in the units you're working with and learn the language of the units you're treating.

 

REFERENCE

Neurotoxins: Now and in the Future; Medscape article, Sept 9, 2009; written by Gary D. Monheit, MD (free registration required)

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