Biotech Values

[DewDiligence]

Gary Borodic, MD, is one of the world’s leading experts
on Botox and medical uses of botulinum toxin. This article
addresses the recent scare from a rodent study and an FDA
warning for pediatric patients. (Although no date is shown,
this article came out a few days ago.)

http://www.allure.com/magazine/2008/05/botox

>>
Botox on the Brain?

BY JOAN KRON

When Botox was first used to relax frown lines, the notion of injecting anything related to botulism into your forehead seemed crazy. But by 2002, when Botox Cosmetic was approved by the FDA to treat forehead lines, consumers as well as doctors had become convinced of its safety.

To date, it's estimated that over one million people have used Botox to relax their forehead frown lines temporarily. But new fears about the substance surfaced recently after reports about an Italian study in the April 2 issue of the Journal of Neuroscience.

It revealed that when botulinum toxin, type A (the active ingredient in Botox), was injected into one side of adult rats' brains, minute particles of protein in the toxin were found in the other side of the brain. Tiny particles also traveled to the rats' brains after the substance was injected into their whiskers.

Although the shots consisted of purified botulinum toxin—not, according to the study author, "a commercial preparation" of the substance (such as Botox)—not surprisingly, many Botox users panicked when media reports of the study questioned whether this meant that Botox could cause brain damage, such as dementia or Alzheimer's.

The study, however, did not suggest that. "I don't think fear is warranted," said Matteo Caleo, a coauthor of the study and a neuroscientist at the Neuroscience Institute of the National Research Council in Pisa. "I would not recommend that someone stop treatment." However, he adds that his area of expertise—and the purpose of his study—is not Botox safety, and that "additional work is needed. It is important to get more insight into this new aspect, in order to [understand] the spectrum of biological activity of a drug that is widely used."

American doctors with long experience treating patients with Botox are not alarmed by the study. "There is nothing in this paper that says these injections will damage neurons or that there are long-term side effects," says Gary Borodic, a Boston ophthalmologist and senior surgeon at Harvard. (He has no association with Allergan, the manufacturer of Botox and Botox Cosmetic.) "The paper deals with the mapping of botulinum activity on the nerve cells, which is a scientific study. It's not a safety study, many of which have previously been conducted in large scales for many indications."

Botulinum toxin at full strength is a deadly poison that can depress breathing, but it is highly diluted in Botox and Botox Cosmetic. Borodic, one of the first physicians to study Botox, has treated patients with neck spasms, eye twitches, and crossed eyes—as well as cosmetic conditions—with the substance since it was first approved by the FDA for clinical trials in the 1980s.

"Medical patients get several hundred units of the drug at one time," Borodic points out, whereas cosmetic treatments "require only a fraction of that—20 to 40 units." Although the amount of neurotoxin administered in the Italian experiment was not excessive for rodents, Caleo explains, it is impossible to compare the concentrations to those used in people, because rats' muscles are so much smaller than humans', and because every species has a different and unknown rate of uptake of the toxin.

Caleo is not worried about cosmetic doses of Botox, but is concerned about excessively large doses of toxin in children with cerebral palsy, an off-label use that has caused problems, including at least one death. (Botox Cosmetic is approved only for adults 18 to 65.)

Botox is supported by large-scale clinical studies and hundreds of scientific articles. And one small study in rodents cannot discount decades of safe use—with a few exceptions—in humans, says Borodic. "The drug has a proven safety record for cosmetic injections," says Borodic. "In all the time it has been in use, we have seen no chronic negative effects."

That isn't to say it's foolproof, he adds—there have been cases of eye drooping after injections in the forehead, which almost always resolves itself over a period of several weeks. But "there are no reports of any effects on the central nervous system… such as dementia, seizures, or degenerative neurological disease after years of repeated dosing in many thousands of patients." And as far as risk of death from Botox Cosmetic, the FDA confirmed that there has never been a reported death where a causal link to Botox Cosmetic was established.

Caleo points out that, in his findings, the fact that some tiny amount of protein remained in the brain "could be good from a therapeutic point of view. This may have a beneficial effect, making the toxin last longer or reducing the severity of headaches. The exact consequences we cannot tell, but it's worth investigating."

Borodic's opinion is similar. "The good news about the study," he says, is that it shows "the toxin might someday be used to treat brain diseases like Parkinson's, dementia, and epilepsy"—a condition being studied with high doses by the Italian group. "It would a shame if people campaigned against it. This study has been blown out of proportion and may scare people unnecessarily."
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