Researchers have found that botulinum neurotoxin type A--more commonly known as Botox--can migrate into the central nervous system after it's injected into the skin. The discovery raises new questions about how the toxin works and what unintended consequences it may have.
Produced by Clostridium botulinum, a common soil bacterium, botulinum toxin is one of the most poisonous substances on Earth. The toxin cuts off communication between nerve cells by destroying SNAP-25, a protein that controls the release of neurotransmitters. The disruption paralyzes the muscles controlled by the nerve cells. But these same paralyzing properties allow doctors to treat strabismus (or "crossed" eyes), migraines, and the chronic and severe muscle spasms that accompany some nervous system injuries or diseases, such as cerebral palsy. Plastic surgeons also use small doses to paralyze facial muscles, thereby making lines and wrinkles less visible.
Matteo Caleo, a neuroscientist at the Consiglio Nazionale delle Ricerche (National Research Council) in Pisa, Italy, and colleagues were evaluating another potential use of the toxin: treating epilepsy. But when studying its effects on epileptic mice, they noticed evidence of the toxin on both sides of the animals' brains, even though they'd injected it on only one side.
Using doses analogous to those prescribed in humans, Caleo's team then injected botulinum into the eyes, whisker pads, and brains of normal mice and rats. They traced the toxin's wreckage--the cleaved SNAP-25--to see where and how it moved through the nervous system. In the case of botulinum type A, the kind used in Botox, they found that wreckage along nerves originating from the injection site and in neighboring nerves. The toxin even reached part of the brain stem.
"The discovery was quite serendipitous ... and surprising," says Caleo. "A significant portion of the toxin is active where it's not intended to be."
The experiment is the first to show that botulinum migrates, says neuroscientist Christopher von Bartheld of the University of Nevada School of Medicine in Reno.
The study's results, published 2 April in The Journal of Neuroscience, come only weeks after the U.S. Food and Drug Administration began investigating widely publicized reports of Botox-related deaths. Although von Bartheld admits it can be tricky to set a safe dose for medical and cosmetic uses, he says there's no need for alarm: "Botox has been used for more than 25 years with very few complications, unless you overdose. ... I don't think fear is warranted." He adds that the toxin's ability to spread might have an upside, allowing doctors to treat brain-based disorders such as epilepsy.