MIRABEL - clinic for aesthetic, clinical dermatology and venereology

What is BOTOX ?

Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals. When introduced intravenously in monkeys, type A (Botox Cosmetic) of the toxin exhibits an LD50 of 40-56 ng, type C1 around 32 ng, type D 3200 ng, and type E 88 ng, rendering the above types some of the most powerful neurotoxins known. Popularly known by one of its trade names, Botox or Dysport, it is used for various cosmetic and medical procedures.

Medical uses.

Although botulinum toxin is a lethal naturally occurring substance, it can be used as an effective and powerful medication. Researchers discovered in the 1950s that injecting overactive muscles with minute quantities of botulinum toxin type-A would result in decreased muscle activity by blocking the release of acetylcholine from the neuron by preventing the vesicle where the acetylcholine is stored from binding to the membrane where the neurotransmitter can be released. This will effectively weaken the muscle for a period of three to four months.

In cosmetic applications, a Botox injection, consisting of a small dose of botulinum toxin, can be used to prevent development of wrinkles by paralyzing facial muscles. As of 2007, it is the most common cosmetic operation, with 4.6 million procedures in the United States, according to the American Society of Plastic Surgeons. Qualifications for Botox injectors vary by county, state and country. Botox cosmetic providers include dermatologists, plastic surgeons, aesthetic spa physicians, dentists, nurse practitioners, nurses and physician assistants. The wrinkle preventing effect of Botox lasts for approximately three to four months, up to six months.

In addition to its cosmetic applications, Botox is currently used in the treatment of spasms and dystonias, by weakening involved muscles, for the 60-70 day effective period of the drug. The main conditions treated with botulinum toxin are:

• Cervical dystonia (spasmodic torticollis) (a neuromuscular disorder involving the head and neck)
• Blepharospasm (excessive blinking)
• Severe primary axillary hyperhidrosis (excessive sweating)
• Strabismus (Squints)
• Achalasia (failure of the lower oesophageal sphincter to relax)
• Local intradermal injection of BTX-A is helpful in chronic focal neuropathies. The analgesic effects are not dependent on changes in muscle tone.
• Migraine and other headache disorders, although the evidence is conflicting in this indication

Other uses of botulinum toxin type A that are widely known but not specifically approved by the FDA (off-label uses) include treatment of:

• Pediatric incontinence, incontinence due to overactive bladder, and incontinence due to neurogenic bladder.

• Anal fissure
• vaginismus To reduce the spasm of the vaginal muscles.
• Movement disorders associated with injury or disease of the central nervous system including trauma, stroke, multiple sclerosis, Parkinson's disease, or cerebral palsy
• Focal dystonias affecting the limbs, face, jaw, or vocal cords
• TMJ pain disorders
• Diabetic neuropathy
• Wound healing
• Excessive salivation
• Vocal cord dysfunction (VCD) including spasmodic dysphonia and tremor
• Reduction of the Masseter muscle for decreasing the apparent size of the lower jaw

Treatment and prevention of chronic headache and chronic musculoskeletal pain are emerging uses for botulinum toxin type A. In addition, there is evidence that Botox may aid in weight loss by increasing the gastric emptying time.

Biochemical mechanism of toxicity.

The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to cleave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for vesicle fusion that releases neurotransmitters from the axon endings (in particular Acetylcholine). Botulinum toxin specifically cleaves these SNAREs, and so prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters.

Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and 2-pam-chloride) will increase mortality by enhancing botulin toxin's mechanism of toxicity. Attacks involving botulinum toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when a sample of the agent is tested. Furthermore, botulism symptoms develop relatively slowly, over several days compared to nerve agent effects, which can be instantaneous.