A compound that strongly inhibits botulinum neurotoxin has been identified by researchers.
The compound – called nitrophenyl psoralen (NPP) – could be used as a treatment to reduce paralysis induced by botulism.
There is no FDA-approved antidote for botulinum neurotoxin (BoNT). Psoralen derived drugs are approved by the U.S. Food and Drug Administration, which would likely hasten the drug approval process for NPP, according to the scientists.
Their study, published in Applied and Environmental Microbiology, a journal of the American Society for Microbiology, found there have been monoclonal antibodies targeting circulating botulinum neurotoxins in clinical trials but effectiveness was restricted by a narrow window for treatment.
Researchers identified the enzyme in botulinum neurotoxin that damages neurons, causing paralysis. They then screened a library of more than 300 natural compounds from extracts of Indian medicinal plants 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 Bal Ram Singh, Professor and Director at the Botulinum Research Center, Institute of Advanced Sciences in Dartmouth, MA.
Although fewer than 200 botulism cases are reported worldwide each year, they cost more to treat than all the Salmonella outbreaks that occur, making botulism the most expensive form of food poisoning, added Dr. Singh.
Four infants in Texas recently developed botulism poisoning after being given pacifiers containing or dipped in honey. The children, all less than a year old, had to be admitted to hospitals for life-saving treatment.
Current therapy for botulism involves respiratory supportive care and administration of antitoxin.
The team tested NPP’s activity in vitro and in cell culture against botulinum neurotoxin type A, which is the most potent among the seven serotypes of botulinum toxin. NPP type A had powerful anti-botulinum toxin activity with low toxicity to human cells.
Financial support for the study was provided by the U.S. Department of Defense and Maryada Foundation.
Clostridium botulinum is a bacterium that produces botulinum toxins under low-oxygen conditions. Spores produced by Clostridium botulinum are heat-resistant and in the absence of oxygen they germinate, grow and then excrete toxins. These toxins are one of the most lethal substances known and can block nerve functions and lead to respiratory and muscular paralysis, according to the World Health Organization.
Symptoms are not caused by the bacterium but by the toxin it produces. They usually appear within 12 to 36 hours after exposure. The disease can be fatal in 5 to 10 percent of cases.
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