A new study finds new evidence that botulinum toxins – including those used in the popular drug Botox, may migrate from the site where its been injected to elsewhere in the body.

Botulinum toxins are among the deadliest substances on Earth, and two specific toxins — including Botox — have multiple uses for treating many neuromuscular conditions, including frown lines, disabling muscle spasms and migraine headaches.

The botulinum toxins cancel nerve signals to the muscles, creating paralysis that can last for months. Given its extraordinary toxicity, doses are typically measured in trillionths of a gram, and targets are carefully chosen to silence only the desired motor nerves.

When these toxins were first approved, the U.S. Food and Drug Administration did so with the understanding that they did not move from the injection site. However, this has always been a concern, say researchers at the University of Wisconsin-Madison, who have now published a study providing proof that these toxins can jump between neurons (nerve cells) in a lab dish.

The study looked at mouse neurons in wells connected by tiny channels that allow growth of axons — the long fibers that neurons use to communicate. In tests of two botulinum toxins, the researchers saw toxin molecules entering the injected cell, as expected.

Once inside a neuron, botulinum toxin cleaves proteins responsible for fusion of chemical containers, known as vesicles, with the plasma membrane. This fusion event releases chemical signals that underlie communication with muscles, and the inability to fuse leads to the temporary paralysis caused by botulinum toxin.

Using antibodies to identify fragments of the damaged proteins, the researchers showed that toxin molecules were moving to nerve cells in wells that had not initially received the harmful molecules.

According to the study's lead author, Edwin Chapman, this research represents the first irrefutable evidence that the powerful toxin can jump between neurons.

"Every time one fraction of the toxin acts locally (on the first nerve cell it contacts), another fraction acts at a distance," says Edwin Chapman, the study’s lead author. "It's unknown how far they travel, which likely depends on the dose of toxin and other factors,” he added.

He is hoping that future research may find a way to genetically engineer the Clostridium bacteria, which makes the botulinum toxin, so that it can only enter the local pathways, and not spread beyond them to other places in the body.

"I have a hard time imagining that any physician is going to want to inject something they know can move about when they have an option to use something that stays put," Chapman says. "It's an exciting prospect, supplanting a $2 billion drug with a safer drug," he adds, referring to the study's findings, which appear in Cell Reports.