In this dossier dealing with beauty in relation to muscles, a substance occupies a prominent place. Its effect to revolutionize aesthetic medicine, and by way of consequences beauty. Cosmetics therefore had to take an interest in it. Back on the fabulous history of the botulinum toxin also known as Botox.
We just cannot start this chapter without mentioning the reference substance: Botox™. The use of Botox™ for beauty purposes is a quite particular story. It is all derived from an older field: the neuromuscular junction. We owe the role and significance of this structure also called “motor plate” to Claude Bernard. The great physiologist found out that muscle contractions originated in the nerve transmission in the neuromuscular junction. He showed muscle contractions could be inhibited with curare. It is this mechanism that indirectly ended up generating Botox™. Indeed, in the late 19th century, a disease called botulism, one of whose symptoms was paralyzed muscles, was rife. It was later shown that this disease was caused by a bacterium which secreted a substance responsible for these symptoms: botulinic toxin. Botulinic (or botulinum) toxin is secreted by Clostridium botulinum, the bacterium responsible for botulism. This protein with neurotoxic properties is the most powerful poison known so far (DL50 1 to 2ng/kg). It was discovered in 1895 by Van Ermengen. Its use was long reserved for therapeutic purposes in particular diseases. Botulinum toxin has an antagonist effect on neuromediators. It inhibits the release of acetylcholine in the myoneural junction and the parasympathetic system. It paralyzes motor nerves and leads to flaccid paralysis. All this is related to the fusion between acetylcholine vesicles and the membrane of nerve cells, by acting on a particular complex: the SNARE proteins. SNAREs contribute to the fusion between the presynaptic vesicle and membrane. By acting on this mechanism, the acetylcholine receptors in muscle cells remain empty and the muscles do not contract.
What does this have to do with beauty? It is actually simple: due to a serendipity phenomenon, its effects in aesthetic treatments were discovered pretty late – and by chance. Although experts had no information about the structure of the skin, they suspected a relationship between the skin and the muscles. As a reminder, the skin is attached to superficial skin muscles by a network of collagen filaments that can contract. Every time the muscle contracts, it draws on these filaments, which get shorter, and all this draws on the skin. As a result, the latter gets marked with wrinkles and ends up sagging. So, if we can reduce the movement of muscles, we should be able to counter this process.
Another way to counter this phenomenon is to target the contraction of collagen fibres – a mode of action the cosmetics industry also adopted. It was called “fibrillary contraction inhibition”. Some product are based on it.
But let’s get back to our Botox™. The confirmation of the relevance of muscle contraction inhibition for beauty purposes was unexpected, as it came from a related field: ophthalmology. Back in the 1960s, Dr Alan B. Scott, an ophthalmologist, started injecting botulinum toxin in monkeys, successfully using its relaxing effects on muscles to develop a strabismus treatment. Since the results were promising, botulinum toxin soon became the reference toxin in research laboratories all over the world. Other research work showed that the benefits of this drug went far beyond ophthalmology, as it temporarily relieved patients suffering from various spasms, including facial spasms. Study after study, other potential uses emerged. But the most revolutionizing discovery, and by far, was made by accident when Dr Jean Carruthers, a Canadian ophthalmologist, noticed her patients with blepharospasm started to lose their frowning wrinkles. In 1992, together with her dermatologist husband, they published a study in the Journal of Dermatologic Surgery and Oncology in which they claimed that “treatment with C. botulinum-A exotoxin is a simple and safe procedure” to treat eyebrow wrinkles. Dermatologists immediately took note of this, and in 1997, Botox was so widely used that the country was temporarily out of stock. The FDA approved new batches and an NDA for this application was issued in 2002.
As a consequence, this substance invaded medical practices the world over and undeniably became the reference substance. Several pharmaceutical specialties were developed, and the market leader, Allergan, who had purchased the rights for use from Scott to this aim, became the leading manufacturer on this segment.
What about cosmetics?
Botox does have obvious limits as regards its cosmetic use.
- First, by nature, it is a powerful neurotoxic substance, so its use in over-the-counter products is banned.
- In addition, Botox should be administered very precisely in the muscle targeted to reach the neuromuscular junction. This requires an experienced operator to make an injection to specifically reach the area wanted. This is done by a doctor, which is obviously incompatible with cosmetics.
Something else will therefore have to be found. But given the interest and enthusiasm for this purpose, the solution will not be long in coming.
Thanks to Mouna Ghoul from Allergan for her invaluable help.