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Botox May Move From Face to Brain, Study in Rats Says (Update1)

By Elizabeth Lopatto

April 1 (Bloomberg) -- Botulinum neurotoxin type A, sold as Allergan Inc.'s Botox remedy for wrinkles, can move from its injection site to the brain, a study shows.

Scientists injected rats' whisker muscles with botulism toxin. Tests of the rodents' brain tissue found that botulism had been transported to the brain stems, the researchers said in the Journal of Neuroscience published April 2.

Botox is Allergan's biggest product, with $1.21 billion in sales last year. The drug, approved in 1989, became fashionable among aging celebrities seeking to smooth facial wrinkles and is used to treat some neurological disorders. The U.S. Food and Drug Administration is investigating whether patients contracted botulism, a muscle-weakening illness, from Botox and Myobloc, a product from Solstice Neurosciences Inc.

``The idea that there could be some transmission of this to the central nervous system needs to be followed up,'' said Mathew Avram, the director of Massachusetts General Hospital's Dermatology, Laser and Cosmetic Center, in Boston, in a telephone interview today. ``But this treatment has been used on millions of people for years, and we're not seeing major central nervous system uses with it.''

Botulism neurotoxin can disrupt nerve cells' ability to communicate and may change spinal cord circuitry, the authors wrote in the study.

Rodents, Not Humans

Mouse and rat physiology is different from that of humans, so the results may not predict what happens in people, Avram said. He wasn't involved in the study.

The study isn't conclusive, and because it contradicts previous findings, more work is necessary, according to an Allergan spokeswoman. The company is based in Irvine, California.

``The authors used a laboratory preparation of botulinum toxin and did not use Botox, and data suggest that different preparations of botulinum toxin react differently in both the laboratory and in clinical practice,'' said the spokeswoman, Caroline Van Hove, in an e-mailed statement.

Myobloc is botulinum neurotoxin type B, a different type of botulinum than studied, said Edgar Salazar-Grueso, chief medical officer of Solstice Neurosciences, in a telephone interview today.

``We are aware from monkey studies already published that toxin A migrates more than B,'' Salazar said. ``Monkeys are more like humans than rodents, so these findings we're observing are consistent.''

FDA Evaluation

Scientists injected botulism toxin into one side of the hippocampus in each rodent brain, and into their superior colliculus, a visual center. From one side of the hippocampus, the toxin migrated to the opposite. From the visual center, the drug went to the animals' eyes.

The effects of the injection into the hippocampus were still present six months later, the scientists wrote.

The FDA is evaluating reports of breathing difficulties and death after use of Botox and Myobloc, according to a posting in February on the agency's Web site. Many of the most serious cases involved children who received the injections to treat arm and leg spasms associated with cerebral palsy, a use not approved by the FDA.

Prescribing literature for Botox and Myobloc now carries warnings about the risk of breathing and swallowing difficulties in patients with neuromuscular disorders. The FDA said the new data suggest that life-threatening side effects may occur in patients with other conditions, including children with cerebral palsy.

Large Doses

Higher doses of Botox are injected to treat limb spasms in children with cerebral palsy in about 60 countries. Some U.S. doctors use it for this purpose, though Allergan doesn't market it in the U.S. for the unapproved use. A typical cosmetic dose is about 10 times less than a dose for cerebral palsy, Avram said.

``The FDA was investigating Botox in situations where large amounts were used,'' Avram said. ``Those tend to be very young children with massive doses. I don't know that this study relates to that.''

Botulism, which can also be spread through contaminated food or wounds, is caused by a bacterium called clostridium botulinum, according to the U.S. Centers for Disease Control and Prevention, in Atlanta. About 110 cases are reported in the U.S. each year.

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