Botox, or Botulinum neurotoxin type-A, is most commonly known for its cosmetic use as a smoother of wrinkles. But research my colleagues and I just published may put a frown on the face of even its most avid users because we’ve shown how this extremely powerful neurotoxin travels into the central nervous system from injection sites on the face.
Botulinum is the pathological agent causing botulism, a rare and potentially fatal paralytic disease. It is capable of blocking nerve-muscle communication, which is how it causes paralysis for an extended period of time (up to four months in humans).
In research we recently published in The Journal of Neuroscience, my collaborators and I were able to visualise single molecules of Botox travelling in our nerves.
The wonder drug
Botulism was discovered in the 1820s during an investigation of the deaths of some people who had eaten blood sausage. Aside from its cosmetic use, this bacterial toxin is used to treat a number of muscular conditions such as strabismus (misaligned eyes), cerebral palsy (muscle incoordination and weakness) and even to stop excessive sweating. Other uses being investigated include the treatment of hayfever and urinary incontinence.
In highly diluted quantities, the protein marketed as Botox is able to temporarily paralyse muscles (the length of time varies but it’s generally three to six months), seemingly without side effects. That’s unless it’s incorrectly administered, of course.
And while it might be used in small quantities, Botox is actually big business: its worldwide market is forecast to reach almost US$3 billion by 2018.
That’s because since its approval for cosmetic use in 1992, Botox has became commonplace. It has escaped Hollywood and become mainstream; former Queensland premier Anna Bligh, for instance, famously admitted to using it while in office.
The good news is that Botox has shown itself to be remarkably safe, despite its gloomy origin as the most potent neurotoxin known to mankind.
Into the nervous system
My team was not the first to detect botulinum in the central nervous system, but this is the first time anyone has been able to characterise the pathway hijacked by the toxin to get there.
We found that following entry into nerve cells that control muscles, the toxin is packaged by a process called autophagy, during which cells encapsulate proteins and other material present in its cytoplasm (the fluid inside the cell), and dispose of them via degradation, which entails the proteins being chopped in little pieces (similar to what happens during digestion).
Large structures called autophagosomes, containing the toxin travel all the way to the central nervous system where they fuse with a dump for these degraded cells. But some of the Botox escapes this degradative pathway by a mechanism that remains to be established.
Another remarkable thing we found is that it travels at around one micron per second. It takes only a few hours for Botox to travel from a forehead injection to the central nervous system.
Should you be worried?
Despite our findings, people who have had Botox injections should take comfort that in more than 20 years of use, no long-term side effects have been discovered. And no reports of systemic problems have emerged despite the significant number of people who have received treatment. So despite being a neurotoxin, Botox is still safe to use but only at highly diluted concentration.
Our finding may actually open another door for Botox’s remarkable ability to be used to treat a number of conditions. We hope to take advantage of the sneaky mechanism Botox uses to escape and roam the central nervous system to try to develop drugs for certain viral infections.
The brain is normally protected from viruses and other pathogens by the blood brain barrier. But some specialised viruses, such as West Nile virus and rabies, are able to bypass the blood brain barrier by accessing the parts of the brain hidden inside our nerves.
Now that we have started to understand how Botulinum toxin is able to make the crossing, we hope to find new therapeutic avenues against these neuropathic pathogens.