Wrinkles Gone? New Uses Studied for Botox
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[Warning -- a few "icky" medical conditions are discussed.
This article is not for the squeamish. (Or ... the "of course I will be young, healthy, and beautiful forever" - type).
Jon.]
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March 2, 2003
By DONALD G. McNEIL Jr.
It is probably premature to declare Botox the penicillin of
the 21st century, but the deadly poison turned wrinkle
remover is being put to some startling new uses.
In studies around the world, botulinum toxin is being
tested - often with encouraging results - as a treatment
for stroke paralysis, migraine headaches, facial tics,
stuttering, lower back pain, incontinence, writer's cramp,
carpal tunnel syndrome and tennis elbow.
Scientists are testing its ability to treat morbid obesity
by weakening the muscle that lets food out of the stomach,
to prevent ulcers by weakening the muscles that force
gastric acids into the esophagus and to calm spasms in
vaginal muscles that make sex painful. Botox is rescuing
newborns with clubfoot from surgery and giving patients
with spastic vocal cords back their voices.
Some trials are nearly ready for submission to the federal
Food and Drug Administration; others are small and
preliminary. But the toxin "has enormous potential" for
relaxing muscles and treating some pain, including
headaches, said Dr. Robert B. Daroff, the former editor in
chief of Neurology magazine, who said he does not use
botulinum toxin in his Cleveland neurology practice but
became a believer after seeing migraine patients improve.
Dr. Jean Carruthers, an ophthalmologist at the University
of British Columbia, compared it to penicillin for its
versatility against a wide range of ills, and because it,
too, is an organic product derived from a common bacterium.
With her husband, Arthur, a dermatologist, she was one of
the first to observe, in 1987, that the small doses she
injected to paralyze and relax her patients' spastic eye
muscles also smoothed their brows.
The toxin has many advantages over other paralyzing and
painkilling agents. It acts only where it is injected. It
can be used merely to weaken a muscle instead of paralyzing
it. It lasts for months, but it does wear off, so mistakes
are reversible. In 25 years of use, it has harmed very few
patients, and then only under rare circumstances.
A spokeswoman for the F.D.A. declined to discuss uses that
the agency has not yet formally approved, but said the
toxin was considered "very safe" for approved uses like
making frown lines disappear. There were "some examples
where it was injected in the wrong places, but those
problems were temporary," said Lenore Gelb, referring a
reporter to the drug's warning labels.
The labeling indicates "rare spontaneous reports of
deaths," mostly from pneumonia. Doctors familiar with the
toxin said they seemed to occur in people with undiagnosed
neuromuscular diseases like myasthenia gravis. Also, they
said, some patients who had too much injected into deep
neck muscles temporarily lost their ability to swallow and
had to be fed by gastric tubes. But to give a normal
patient a fatal dose would require injecting at least 35
vials, Dr. Carruthers said.
"Every medical specialty is finding a niche for this drug,"
said Dr. Richard G. Glogau, a dermatologist at the
University of California at San Francisco who in 2000
published a study showing that his wrinkle treatments were
also curing his patients' migraine headaches.
Because it can even paralyze glands, the toxin could find
uses as an injectable deodorant and a treatment for flop
sweat.
At Ludwig-Maximilian University in Munich, panelists who
sniffed circles cut from the sleeves of T-shirts of 16 men
who had been injected with botulinum toxin in one armpit
and saline solution in the other found the toxin armpit
odor less unpleasant.
Several studies have shown reductions in hyperhydrosis,
which is not mere clammy palms but the dripping-faucet kind
of sweating that rots shoe soles and ruins business deals
and love lives.
The toxin is "one of the most amazing compounds we've seen
in the last two decades," said Dr. Marc Heckmann, a Munich
dermatologist who led two sweat-control studies. He
compared it in importance to the discoveries of
corticosteroids and chemotherapy.
Now virtually any muscle that can spasm, producing painful
or embarrassing reactions, is being experimented upon.
Doctors are devising new deep-body injection techniques:
syringes attached to flexible scopes or to probes that
detect electrical impulses in muscles.
Three months ago, Beatrice F. Brunger, 79, of Chicago was
suffering from incontinence, and had suffered for three
years. As often as four times a night, she had to get up as
the muscle walls of her bladder went into spasms - a common
cause of incontinence among the elderly.
"Then I couldn't get back to sleep," Mrs. Brunger said. "My
strength was going steadily downhill. I wouldn't go out for
lunch or dinner or a movie - I was just too tired."
Detrol and Ditropan, the usual drugs for the condition, did
not work. Normally, Mrs. Brunger would have faced a
daunting operation: up to three hours of surgery to make a
hole in the side of her bladder and build a "reserve tank"
of intestine material.
Instead, Dr. Gregory T. Bales, a urological surgeon with
the University of Chicago Hospital, used a cystoscope with
a camera and a minute syringe to travel up her urethra and
inject the inside walls of her bladder with three vials of
Botox - more than triple the amount used to smooth forehead
wrinkles.
"It takes five minutes," he said. "We make 20 to 25
injections. A full bladder is about the size of a
cantaloupe, and each injection takes care of about the size
of a quarter."
Mrs. Brunger said she came home an hour later, had no pain,
and since then has slept through the night. The only side
effect is that, during the day, it takes somewhat longer to
urinate.
"Botox is neat," Dr. Bales said. "We're doing 15 patients a
day."
The one drawback, he said, is that his study is so new that
he does not know how long it lasts. In cosmetic use, it
wears off in six to eight months.
In Vancouver, British Columbia, Dr. Christine M. Alvarez, a
pediatric orthopedic surgeon, treats clubfoot, a twisting
inward of the heel and toe that affects up to 1 in 500
infants.
In the past, Dr. Alvarez said, she had to slice open their
feet from toe to ankle and cut and rebuild six tendons. The
operation had a high complication rate, robbed the babies
of some of their muscle power and produced stiff gaits.
In the last year, she has instead injected 45 newborns with
botulinum toxin, stretched out their relaxed leg muscles,
put on casts for eight weeks to stabilize them, and then
shifted to night braces as they grew. "Thirty of them are
toddlers now, and walking normally," she said. "It's a huge
change from the surgery."
Last month, in the Annals of Internal Medicine, a team at
the Hannover Medical School in Germany reported that it had
treated a 220-pound man by injecting the walls of his
stomach with toxin to slow the speed at which it emptied.
He felt full even after eating small amounts and lost 20
pounds in four months with no apparent adverse effects, the
team reported.
Another team in Milan that reported success with obese rats
is planning human trials.
In Texas, Dr. Pankaj J. Pasricha, a gastroenterologist at
the University of Texas Medical Branch, has used it to
relax other gastric muscles, such as the esophageal ones
that cause swallowing difficulties and the sphincters that
can close off and inflame gallbladders and bile ducts.
The toxin's use for migraines is in the final stages of
large clinical trials.
Why it works is unclear. In motor nerve endings, botulinum
blocks the release of acetylcholine, which tells muscles to
contract. It wears off slowly as the nerves sprout new end
plates.
For headaches, it seems to work on sensory nerves as well,
blocking pain but not deadening touch. "No one knows why,"
Dr. Daroff said. "It's probably a complex cascade of
effects, like a Rube Goldberg cartoon."
Neurologists were reluctant to accept the evidence because
it fought the paradigm that migraine headaches are caused
by dilation and constriction of cranial blood vessels.
"It took three or four years of flogging the manuscript to
get it published in Headache," said Dr. Carruthers. "All
the neurologists said, `That's ridiculous.' It's not how
they saw the pain working."
Other poisons have medicinal uses. The curare that South
American Indians tipped their darts with is used in
surgery, and West African physostigmine, used in
witchcraft, has been used to treat nervous system problems.
Botulinum toxin does not act like silicon, collagen or the
polymer-collagen blends used against wrinkles; it paralyzes
muscles, while they make flaccid skin plump.
It is an odd fate for a poison that nearly wiped out the
canning industry in the 1930's. When the Clostridium
botulinum bacteria is swallowed, it can multiply in humans,
releasing fatal doses of toxin.
Botox and its competitors are the pure toxin, but in
extremely dilute form.
Although all botulinum toxins are colloquially called
"botox," Allergan Inc. of Irvine, Calif., copyrighted the
name for its Toxin A product. Its competitors are Myobloc,
a Toxin B preparation from Elan Pharmaceuticals, and
Dysport, a Toxin A from Ipsen, a British company.
Each costs $300 to $400 a vial. Scientists and patients
complain about the price, especially since the toxin is a
natural product and the technique of purifying it was
worked out 50 years ago by the Army at Fort Detrick, Md.,
in biological warfare research. Still, it is cheap compared
with surgery.
Allergan's Botox was approved in 1989 as an orphan drug for
use against crossed eyes and eyelids that clenched closed,
leaving a victim functionally blind, and against severely
spastic neck muscles.
In 2002, it was approved for use on frown lines.
Allergan
has clinical trials under way to test it against headaches,
excessive sweating and spasticity in stroke victims, whose
muscles may dig their nails into their palms and make it
impossible for them to feed or dress themselves.
Allergan acquired the Army's old supply of toxin in 1991
and started making its own in 1997. Worldwide sales last
year were $440 million.
"Ten years ago, I doubt that any colorectal surgeon would
have considered using botulinum toxin because it had the
`deadly poison' label," Dr. Glogau said. "But now anybody
who has skeletal muscle in his practice begins to think,
`How can I use this?' It's not scary anymore."
Copyright 2003 The New York Times Company. |
