Beating One of the World’s Most Powerful Poisons

Clostridium botulinum paralyzes muscles and stops breathing, but scientists have found a way to halt this process in the body before it causes too much damage. Keep reading to learn more!

Sections:
  1. Learn About Clostridium botulinum
  2. How Scientists Beat the Poison
  3. Testing the Strategy
  4. Implications
(TL;DR at the bottom 😊)
Approximate Read Time: 3 minutes!

Learn About Clostridium botulinum

Clostridium botulinum (botulinum toxin) is a toxic bacteria that causes botulism, a process that paralyzes muscles and causes the inability to breathe. The toxin is produced by bacteria that grows in poorly preserved foods and in infected wounds.

The botulinum toxin makes its way into nerves and tears apart proteins that are vital for nerve signaling. Essentially, instead of killing the neurons, this toxin renders them unable to function. 

Artist rendition of the botulinum toxin.

Poison by botulinum toxin is actually quite rare (less than 200 reported US cases per year), however the toxin has the potential to become an incredibly powerful bioweapon.

In small and controlled quantities, botulinum toxin is used to control muscle spasms and smooth wrinkles (as done in the well-known procedure, Botox), but in large quantities, the toxin is deadly.


How Scientists Beat the Poison

Development of the treatment to beat botulinum toxin was driven by microbiologist Shin-Ichiro Miyashita at the Tokyo University of Agriculture. 

Miyashita and his team took the natural form of the toxin and made three genetic changes to it. An active drug, an antibody derived from alpacas, was also engineered into the toxin. This produced an altered form of the toxin that chases the original deadly toxin into nerves and renders it harmless. This is an incredible use of a toxin-based delivery platform!

The toxin-based delivery platform consists of the modified botulinum toxin at upper left (protease domain in gold, translocation domain in blue, and receptor-binding domain in purple) and the nanobody (the pink tag). When this nanobody-toxin fusion protein binds to the receptor (cyan) on the neuron surface, the cell takes it in through the process of endocytosis, corralling the fusion protein inside a vesicle (light green circle). The toxin’s protease domain, carrying the nanobody, then crosses into the interior of the cell. (Image: Sicai Zhang/Dong Lab, Boston Children’s Hospital)

Essentially, the researchers used the toxin’s strength (that it can deliver proteins across cell membranes) against itself!

“One barrier to treatment has been getting across the cell membrane, which is difficult for protein drugs. The other is targeting specific cell types, and in this case specificity toward motor neurons and nerve terminals. We took advantage of the fact that botulinum neurotoxins naturally target motor neurons and can deliver a protein cargo across cell membranes.”

Shin-Ichiro Miyashita, PhD

Testing the Strategy

This botulinum toxin treatment was tested successfully in mice, guinea pigs, and macaque monkeys. In these tests, there was no detected toxicity in the treated animals at doses of the toxin that were originally deadly.

The scientists are currently preparing this treatment product for approval from the US Food and Drug Administration


Implications

This treatment described here is the first treatment developed and successfully tested to reverse the paralyzing effects of botulinum toxin. This treatment would save patients from discomfort and long recovery time on a ventilator.

It’s important to note that even though this treatment strategy proved effective in animals, the toxin manifests differently in humans. Human patients will likely still need an additional antitoxin treatment to remove leftover toxins from their blood.

This treatment strategy is not an end all be all for botulinum toxin treatment, but it is a large step towards improving care for botulism!

What are your thoughts on this new botulinum toxin treatment?

Thank you for reading this piece. I hope you enjoyed it & will further ponder the knowledge it brings to light. I encourage you to leave a comment and/or start a discussion in the section below! 

Feel free to contact me at brainsproutblog@gmail.com and follow the blog @brainsproutblog on Instagram or Twitter for updates!


TL;DR
  • Clostridium botulinum (botulinum toxin) is a toxic bacteria that causes botulism, a process that paralyzes muscles and causes the inability to breathe
  • The botulinum toxin makes its way into nerves and tears apart proteins that are vital for nerve signaling
  • Scientists genetically engineered the natural form of the toxin to produce an altered form of the toxin that chases the original deadly toxin into nerves and renders it harmless (toxin-based delivery platform!)
  • This botulinum toxin treatment was tested successfully in mice, guinea pigs, and macaque monkeys
  • This treatment would save patients from discomfort and long recovery time on a ventilator
Read more (sources)!
  1. https://www.sciencemag.org/news/2021/01/new-strategy-fight-world-s-most-potent-poison-passes-first-tests-animals 
  2. https://stm.sciencemag.org/content/13/575/eaaz4197 
  3. https://discoveries.childrenshospital.org/botulism-treatment-delivery-platform/ 
Image Sources:
  1. https://www.sciencemag.org/news/2021/01/new-strategy-fight-world-s-most-potent-poison-passes-first-tests-animals
  2. https://discoveries.childrenshospital.org/botulism-treatment-delivery-platform/ 

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