The following Azura Skin Care article is provided by guest blogger Sarah Handzel, BSN, RN, published in collaboration with Azura SKin Care Center’s Jennie Kowaleski, PA-C.
It’s hard to imagine anyone that hasn’t heard of Botox, Dysport, or even Xeomin by now. Most people know they’re used to help smooth out wrinkles and age lines, but many don’t know how these products came to be or what they really do. So how were these products discovered and developed? How do they actually work? Are they just used cosmetically, or are they used for other reasons, too? In a three-part series, I’ll answer those questions so you can learn more about these valuable and versatile products!
Early Discovery
While Dr. Justinus Kerner (1) originally described effects of eating sausage tainted with a then-unknown toxin in the early 1800’s, the history and research of what is today known as Botox really took off in the late 1800’s. Three band members playing in a club in Belgium ate some rare-cooked, salted ham. Sadly, after they ate the ham, all three band members developed paralysis – the inability to move – throughout their bodies and eventually died. Recognizing that something from the food might have caused this unexpected event, Professor Emile Van Ermengem started investigating. The problem was eventually identified in 1895 as Clostridium botulinum (2), a bacterium commonly found in soil that makes potent neurotoxins.
This bacterium was responsible for producing the botulinum neurotoxin itself. Unfortunately for the musicians, they’d eaten food that was contaminated with this toxin and died as a result of its high concentrations – much higher concentrations than we use when treating wrinkles! Interestingly, Clostridium botulinum actually produces 7 different neurotoxins, all with slightly different chemical structures. It wasn’t until 1946 that the ‘A’ strand toxin was actually isolated from the other toxins; it later became the basis for the medication known as Botox.
Further studies of the ‘A’ toxin proved that the it inhibits neuromuscular transmissions. Put simply, it blocks chemical signals sent between nerves and muscles. When these signals are blocked, muscles don’t respond to the nerves and the muscles don’t move. This was confirmed in the 1950s, when Dr. Vernon Brooks became the first researcher to inject the ‘A’ toxin into hyperactive muscle tissue. He found that it prevented the muscle from functioning normally and stopped its hyperactive contractions.
In the 1960s, Dr. Alan Scott (3) used the ‘A’ toxin to treat strabismus – more commonly known as crossed eyes – in animals and then later in humans. The initial results were encouraging. Research continued, and Dr. Scott eventually formed Oculinum, Inc. for the continued study of the ‘A’ toxin using human volunteers. The FDA later approved use of the neurotoxin under the brand name Oculinum in 1989. Initially, Oculinum was only approved for use in humans in the treatment of strabismus and blepharospasm, another eye movement disorder characterized by rapid, involuntary blinking or eyelid spasms.
Scientists continued to research and experiment, and Oculinum was rebranded using the name we all know today, Botox. In 2001, Botox was approved in Canada for the cosmetic treatment of wrinkles at the brow line. It wasn’t until April 15, 2002 that Botox was approved by the FDA for use in the United States. At first, the product was only approved for moderate-to-severe frown lines appearing between the eyebrows. In 2013, Botox was approved for use on crow’s feet. Research continues even today, with more and more therapeutic uses for Botox being found.
Botox Has Competition in Dysport
While research continued, studies were also being done using another derivative of the same neurotoxin used to product Botox. In the 1980s, scientists used the derivative of the ‘A’ toxin to successfully treat two eye muscle spasm disorders. Later, in 1991, it was approved for use for certain muscle spasm disorders in Europe and Asia under the brand name Dysport and eventually made its way to the States.
Both Dysport and Botox have the same molecule that makes up their core chemical structure. The difference is in the proteins that surround and protect that core. There is some debate among researchers about the onset of action of each product – in other words, how fast each product takes to work. Some research seems in show that Dysport may work faster than Botox (4), but this has not been definitively proven. In some studies, Dysport was seen to work within 3-4 days of administration. Unfortunately, the onset of action of Botox wasn’t measured in any of its original scientific studies, so we really can’t compare how fast the two products work until more research is performed using Botox.
Mechanism of Action
We talked a bit above about the way muscles and nerves communicate so if you’re still with me, let’s dive a bit deeper. How do Botox or Dysport actually work once they’re injected into the muscle? First, we’ve got to understand what happens when a muscle contracts in order to product movement.
Normally, the end of a nerve cell – the axon – is located very close to a portion of a muscle. The small space in between the axon and the muscle is called the synapse. When the brain tells a muscle to move, certain chemical messengers are released from the axon. They travel from the axon across the synapse to the muscle, where they attach to specific binding sites. When the messengers attach to the binding sites, the muscle gets the signal to move.
Think of it like tossing a football back and forth between two people. One person is the nerve axon, the other is the muscle, and the football is the chemical messenger. The binding site on the muscle is the hand of the person catching the football.
The first person throws the football. In our example, this means that the nerve axon releases the chemical messenger. The football sails across the yard, i.e. the messenger travels across the synapse. Finally, the second person catches the football in their hand. This is the same as the messenger binding to a site on the muscle itself. Make sense? Again, once the messenger is attached to the binding site on the muscle, the muscle gets the message to move!
So how does this relate to Botox and Dysport? Well, research has shown that the botulinum toxins actually stick to the nerve axons. This prevents the release of the chemical messenger acetylcholine (5). Because no acetylcholine is released from the axon, the muscle doesn’t know to move. There’s a localized muscle paralysis that gradually goes away over time. No one knows how the paralysis actually goes away, but it’s thought that new short lived nerve sprouts (6) form off the axon to release acetylcholine once again into the synapse. All in all, it takes three to four months for these short term connections to form and help to “wake up” the original muscle and nerve allowing them to communicate which is why the effects of both Botox and Dysport last for around that length of time in most people.
Healthcare providers have been using the botulinum neurotoxins for over 30 years to provide therapeutic benefits to people, and more uses for both Botox and Dysport are currently being investigated. In the next blog post, I’ll talk about some of the cosmetic uses of these products and compare them to other medical treatments.
Resources
https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0036-1571849
http://www.fsis.usda.gov/wps/portal/fsis/topics/food-safety-education/get-answers/food-safety-fact-sheets/foodborne-illness-and-disease/clostridium-botulinum/ct_index
http://www.allergan.ca/Assets/pdf/botox_history_and_development.pdf
http://dermatologytimes.modernmedicine.com/dermatology-times/news/modernmedicine/modern-medicine-feature-articles/botox-dysport-share-more-simi?page=full
http://www.britannica.com/science/acetylcholine
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192970/
Sarah Handzel, BSN, RN
Registered Nurse and Freelance Copywriter
Owner, Catbird Writing Solutions, LLC
919-418-1784
catbirdwriting.com
Posts in this Series
Botox and Dysport: Where Did They Come From? How Do They Work?
Cosmetic Uses of Botox and Dysport Compared to Other Treatment Options
Off-Label Cosmetic Treatment Options Using Botox and Dysport
[…] far, we’ve discussed the discovery and history of Botox and Dysport in addition to their typical cosmetic uses compared to other treatment options. In the final […]