Botulinum toxin (BTX) commonly referred to as Botox, is a neurotoxin that is derived from the bacteria Clostridium botulinum. Botox stops acetylcholine (a neurotransmitter) from being released in the neuromuscular junction which causes flaccid paralysis, which is relaxation of the muscles. The neurotoxin is commonly used in cosmetics, and medicine as well as research.
A bacterial infection from Clostridium botulinum causes botulism disease. It is the most lethal toxin, the median lethal dose in humans is 1.3 – 2.1 ng/kg when injected, and 10 – 13 ng/kg when inhaled. As a result, the FDA requires a warning that when locally injected, the toxin could still spread to other areas of the body, resulting in botulism.
There are seven forms of the neurotoxin botulinum. These are types A through G. Botulinum toxin A and B are those which are used in medicine to treat diseases like muscle spasms and used for cosmetics like Botox (made by Allergan).
Botox can be used to treat several disorders. Its ability to relax muscles is used to help with post-stroke and post-spinal cord injury spasticity, head and neck spasms, spasms of the eyelid, limbs, jaw, vagina, and vocal cords. It is also used to relax clenched muscles such as the jaw, urinary tract, bladder, anus, and esophagus. And it is also helpful with correcting improper eye alignment. It is also used to help with hyperactive nerves which can result in excessive sweating, pain, and allergies.
Botox is most commonly used for cosmetic purposes. It is regarded as a safe and effective treatment for the reduction of wrinkles in the face. Botox is injected into the muscles under facial wrinkles and causes the muscles to relax and will produce smooth skin. Results of cosmetic Botox injections are usually seen in about three days after the injection, with the most results seen within two weeks. Results from cosmetic Botox injections typically last for about three or four months before the muscles begin to regain their function, so repeated treatments are required in order to maintain a smooth appearance of the skin.
The toxin botulinum works to paralyze muscles by cleaving proteins that are needed for nerve activation. Botulinum first binds to nerve terminals that use acetylcholine. Then the neuron takes the botulinum into a vesicle. The vesicle will then acidify as it moves farther and farther into the cell which pushes it into the cytoplasm of the cell. Then the toxin cleaves SNARE proteins which prevents the cell from releasing vesicles of acetylcholine. This keeps the nerve from signaling and results in paralysis.
The first complete description of botulism was given by a German medical officer, Justinus Kerner in 1820. He based his description on his clinical observations of “sausage poisoning”. Kerner conducted experiments on himself and animals and concluded that the toxin interrupts signal transmission in the somatic and autonomic motor system, but does not affect sensory signals or mental function. He stated that it is developed uner anaerobic conditions and can be lethal in very small amounts. He also suggested that the neurotoxin could be used therapeutically, and this statement earned him recognition as the pioneer of modern botulinum toxin therapy.
Seventy five years after Kerner made his description of botulism, Emile van Ermengem, a professor of bacteriology, isolated and grew the bacteria, Clostridium botulinum, which was later purified by P Tessmer Snipe and Hermann Sommer.
As the food canning industry grew over the next 30 years, botulism became a public health hazard. In response, a veterinary scientist, Karl Friedrich Meyer, developed ways of growing the bacteria, and extracting the toxin. He also developed a method of preventing the bacteria’s growth, and inactivating the toxin.
During WWII, the US began researching how to weaponize the botulinum toxin. Carl Lamanna and James Duff developed ways to concentrate and crystallize botulinum. Techniques that were later used by Edward J Schantz to create the first clinical product. After the war, Schantz began manufacturing the toxin for experimental use and provided it to other researchers.
The first medical application of Botox was used for helping with eye muscle disorders or strabismus. After researching the effects on monkeys, Alan B Scott applied to the FDA for investigational drug use and injected the first strabismus patients in 1977. He called the drug Oculinum.
Strabismus is a result of imbalanced muscles that rotate the eyes. If one muscle pulls to strongly, or if one has been weakened, then strabismus will result. Botox helps to alleviate this by weakening the stronger muscle. Because muscles adapt to the lengths that they are held, when the toxin wears off, the muscles will still remain functioning as they should after only one injection.
By the 1980’s, botulinum had been used to treat strabismus and nystagmus, eyelid muscles, blepharospasm, facial muscles, and limb muscles. It is the same specificity and molecular tenacity that makes the ingested toxin so deadly, that also makes it incredibly safe when injected directly into a target muscle.
L Andrew Koman was the first to use the neurotoxin to treat the leg spasms that come from cerebral palsy. After these successes, the use of Botox for treating muscular disorders expanded rapidly. It began to be used to treat blepharospasm, torticollis, achalasia, gastro enteric and urinary spasms, muscle spasms from strokes and more.
In 1989, Allergan got FDA approval to begin marketing Oculinum to treat adult strabismus and blepharospasm, using the trademark Botox.
In 1989, a plastic surgeon named Richard Clark, first documented a cosmetic use for botulinum. He recognized that the toxin could be injected to smooth the wrinkles of the forehead and received FDA approval for the cosmetic application of Botox.
Jean and Alistair Carruthers were treating blepharospasm patients when they realised that their patients had diminished frown lines which sparked the popular cosmetic use of Botox. In 2002 the FDA approved Botox Cosmetic to treat moderate to severe frown lines.
In 2000, Dr. Binder noticed that patients who had cosmetic injections also had reported relief from chronic headaches. Botox actually inhibits the release of certain neurotransmitters and suppresses the central pain processing systems which are responsible for migraines. The FDA approved Botox injections for treatment of migraine headaches in 2010.