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Scientists identify potential antidote to paralysis-inducing toxin that causes botulism

The neurotoxin is the most potent toxin known to exist and is considered a potential bioweapon.

RESEARCHERS IN THE US have identified a compound that strongly inhibits the bacteria botulinum, the most potent toxin known to exist.

The neurotoxin, which occurs naturally, is considered a potential bioweapon because no approved antidote to it exists, although it is usually transmitted to humans through food.

Botulinum toxin is produced by Clostridium botulinum, a soil bacterium that is ubiquitous and hard to kill, and the spores can even survive being boiled.

Botulism can be acquired through routes other than food poisoning too, such as wound contamination or via the colonisation of the digestive tracts of children and infants.

However the discovery of a new inhibiting compound, nitrophenyl psoralen (NPP), as part of a study could change that – and mean a treatment could become available to reduce the paralysis induced by botulism.

Indian plants

Research published in the journal Applied and Environmental Microbiology revealed how scientists at the Botulinum Research Centre made the discovery.

As part of a study, investigators attempted to identify an enzyme within botulinum neurotoxin that damages neurons and causes paralysis.

They then screened a library containing more than 300 natural compounds from extracts of Indian medicinal plants as they searched for enzymes that could neutralize the neuron-damaging activity.

“Using high throughput screening, we identified one of the compounds, nitrophenyl psoralen, as having particularly strong activity against the neuron-damaging enzyme,” said corresponding author Dr Bal Ram Singh, Professor and Director of the Botulinum Research Center.

The team then tested NPP’s activity in vitro and in cell culture against botulinum neurotoxin type A, which is the most potent serotype – a variant of specific form of bacteria – among the seven serotypes of botulinum.

Drug approval

They found that NPP type A had powerful anti-botulinum toxin activity, and a low toxicity to human cells.

“NPP also showed activity to reverse the mouse muscle paralysis induced by botulinum neurotoxin type A,” said Dr. Singh.

Although fewer than 200 botulism cases occur throughout the world every year, they cost more to treat than the millions of salmonella outbreaks that occur.

The research originated from Dr. Singh’s group’s work on biochemical basis of Ayurveda, an herbal medicine system widely used in India.

Psoralen derived drugs are already approved by the the US Food and Drug Administration, meaning the drug approval process for NPP would likely not take long.

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