Botulinum toxin
is a neurotoxin protein produced by the bacterium Clostridium botulinum.
It is one of the most poisonous naturally occurring substances in
the world, and it is the most toxic protein. Though it is highly
toxic, it is used in minute doses both to treat painful muscle spasms,
and as a cosmetic treatment in some parts of the world. It is sold
commercially under the brand names Botox and Dysport for this purpose.
The terms Botox and Dysport are trade names and are not used generically
to describe the neurotoxins produced by the clostridia species.
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History
Between 1817
and 1822 the German physician and poet Justinus Kerner described
botulinium toxin, using the terms "sausage poison" and
"fatty poison", as this bacterium often causes poisoning
by growing in badly handled or prepared meat products. He first
conceived a possible therapeutic use of botulinium toxin. In 1870,
Muller (another German physician) coined the name botulism, from
Latin botulus = "sausage". In 1895, Emile Van Ermengem
first isolated the bacterium Clostridium botulinum. In 1944, Edward
Schantz cultured Clostridium botulinum and isolated the toxin, and,
in 1949, Burgen's group discovered that botulinum toxin blocks neuromuscular
transmission.
By 1973, Alan
B Scott, MD, of Smith-Kettlewell Institute used botulinium toxin
type A (BTX-A) in monkey experiments, and, in 1980, he officially
used BTX-A for the first time in humans to treat strabismus. In
December 1989, BTX-A (BOTOX) was approved by the US Food and Drug
Administration (FDA) for the treatment of strabismus, blepharospasm,
and hemifacial spasm in patients over 12 years old. The cosmetic
effect of BTX-A was initially described by ophthalmologist Jean
Carruthers and dermatologist Alastair Carruthers, a husband-and-wife
team working in Vancouver, Canada, although the effect had been
observed by a number of independent groups. On April 15, 2002, the
FDA announced the approval of botulinum toxin type A (BOTOX Cosmetic)
to temporarily improve the appearance of moderate-to-severe frown
lines between the eyebrows (glabellar lines). BTX-A has also been
approved for the treatment of excessive underarm sweating. The acceptance
of BTX-A use for the treatment of spasticity and muscle pain disorders
is growing, with approvals pending in many European countries and
studies on headaches (including migraine), prostatic symptoms, asthma,
obesity and many other possible indications are ongoing.
Botox is manufactured
by Allergan Inc (U.S.) for both therapeutic as well as cosmetic
use. The formulation is best stored at cold temperature of 2-8 degrees
Celsius. Dysport is a therapeutic formulation of the type A toxin
developed and manufactured in Ireland and which is licenced for
the treatment of focal dystonias and certain cosmetic uses in many
territories world wide. Neuronox is a new type A toxin manufactured
by Medy-Tox Inc (South Korea).
Botulinium Toxin
Type B (BTX-B) received FDA approval for treatment of cervical dystonia
on December 21, 2000. Trade names for BTX-B are Myobloc in the United
States, and Neurobloc® in the European Union.
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Medical uses
Researchers
discovered in the 1950s that injecting overactive muscles with minute
quantities of botulinum toxin type A decreased muscle activity by
blocking the release of acetylcholine at the neuromuscular junction,
thereby rendering the muscle unable to contract for a period of
4 to 6 months.
Alan Scott,
a San Francisco ophthalmologist, first applied tiny doses of the
toxin in a medicinal sense to treat 'crossed eyes' (strabismus)
and 'uncontrollable blinking' (blepharospasm), but needed a partner
to gain regulatory approval to market his discovery as a drug. Allergan,
Inc., a pharmaceutical company that focused on prescription eye
therapies and contact lens products, bought the rights to the drug
in 1988 and received FDA approval in 1989. Allergan renamed the
drug Botox.
Cosmetically
desirable effects of Botox were quickly discovered thereafter when
the frown lines between the eyebrows were observed to soften following
treatment for eye muscle disorders, leading to clinical trials and
subsequent FDA approval for cosmetic use in April 2002. As of 2006,
Botox injection is the most common cosmetic operation in the United
States.
Besides its
cosmetic application, Botox is used in the treatment of
migraine
headaches
cervical
dystonia (spasmodic torticollis) (a neuromuscular disorder involving
the head and neck)
blepharospasm
(involuntary blinking)
severe primary
axillary hyperhidrosis (excessive sweating)
achalasia
(failure of the lower esophageal sphincter to relax)
Other uses of
botulinum toxin type A that are widely known but not specifically
approved by FDA include treatment of:
pediatric
incontinence, incontinence due to overactive bladder, and incontinence
due to neurogenic bladder.
anal fissure
spastic
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
reduction
of the Masseter muscle for decreasing the size of the lower jaw
In the Journal
of Dermatologic Surgery, Eric Finzi claims to have treated clinically
depressed patients with botox. On Good Morning America, he claimed
that by taking away the ability to frown, he was somehow taking
away the ability to feel depressed.
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.
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Side effects
Side effects
can be predicted from the mode of action (muscle paralysis) and
chemical structure (protein) of the molecule, resulting broadly
speaking in two major areas of side effects: paralysis of the wrong
muscle group and allergic reaction. Bruising at the site of injection
is a side effect not of the toxin, but rather the mode of administration.
In cosmetic use, this means that the client will complain of inappropriate
facial expression such as drooping eyelid, uneven smile, loss of
ability to close the eye. This will wear off in around 6 weeks.
Bruising is prevented by the clinician applying pressure to the
injection site, but may still occur, and will last around 7 - 10
days. When injecting the masseter muscle of the jaw, loss of muscle
function will result in a loss or reduction of power to chew solid
foods. All cosmetic treatments are of limited duration, and can
be as short a period as six weeks, but usually one reckons with
an effective period of between 3 and 8 months. At the extremely
low doses used medicinally, botulinum toxin has a very low degree
of toxicity.
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