A new therapy shuts own deadly botulinum neurotoxin

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Botulinum neurotoxin

Botulinum toxin (BOTOX) is a neurotoxic protein produced by the bacterium Clostridium botulinum, it produces one of the most potent toxins on earth and is classified as a potential bioterrorism threat.

The effects are only temporary, but the injections can be done quickly, require no recovery time, and are not as complicated as many other cosmetic procedures for the face.

Symptoms include blurry vision, slurred speech, muscle weakness and difficulty swallowing, and even death by affecting the patient’s ability to breathe.

Lead scientist Kim Janda, Jr. Professor of Chemistry at The Scripps Research Institute (TSRI), said, to discover potential inhibitors of the toxin, researchers screened triazole compounds against the botulinum neurotoxin light chain, a proteolytic enzyme that disrupts neuronal signaling to muscles.

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They hit upon a triazole compound that appeared to forcefully inhibit the toxin light chain in an enzymatic assay.

New Therapy

The scientists had accidentally landed upon a potential new therapy for type A of the neurotoxin, the most common and deadly cause of human botulism, using copper chloride, an inexpensive, readily available metal salt as the active ingredient.

Following, the researchers designed molecules called ligands to act as delivery vehicles for copper into neuronal cells.

The compound extended the animals’ lives, even when they were given lethal doses of the toxin.

Researchers said, the copper therapeutic could provide a more effective therapy than existing approaches to botulism.

Currently, botulism sufferers receive an anti-toxin medicine that can inactivate the toxin circulating in their system, thereby preventing further poisoning.

However, the anti-toxin cannot reverse preexisting paralysis because the toxin acts inside cells. Consequently, disease recovery can be slow, and paralysis may take weeks or months to wear off.

This new therapy can readily enter cells, where it can attack the etiologic agent, a protease, which is responsible for paralysis seen from the neurotoxin.

The researchers also noted that the study further demonstrates the need to explore metals for therapeutic uses.

More information: [JACS]

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