New strategy to fight botulinum toxin - expert available
2021-01-06
(Press-News.org) Related to new research published in the January issue of Science Translational Medicine, Patrick McNutt, PhD, of the Wake Forest Institute for Regenerative Medicine, was part of the research team that demonstrated a new "Trojan horse" approach that produces strong antidotal efficacy in treating lethal botulism in mice, guinea pigs and rhesus macaque monkeys.
Furthermore, in a companion article, an independent team demonstrated that a related drug has robust efficacy in mice.
"This is one of those serendipitous moments in science where two groups, working independently, demonstrate similar results for a long-standing problem," McNutt said. "We are currently modifying this drug to enhance its therapeutic properties against botulism and exploring whether the same approach can be repurposed to treat other neuronal diseases."
In 2010, Konstantin Ichtchenko (New York University School of Medicine) conceived of a novel 'trojan horse' strategy to treat botulism. This strategy is based on using a non-toxic form of BoNT to deliver therapeutic antibodies to paralyzed neurons, blocking wild-type toxin activity and accelerating recovery from paralysis. Over the past decade, Konstantin established collaborations with Patrick McNutt (Wake Forest Institute of Regenerative Medicine), Phil Band (Cytodel, Inc.) and Chuck Shoemaker (Tufts University) to develop and test this new drug in a variety of experimental models.
Botulinum neurotoxins (BoNTs) are a family of bacterial poisons responsible for the clinical disease known as botulism. BoNT acts within nerve terminals to destroy proteins necessary for evoking muscle contraction, causing muscle paralysis that develops into respiratory arrest at lethal concentrations. BoNT is the most poisonous substances known, with median lethal doses that are over a million-fold lower than cyanide.
Because of its extraordinary potency and long duration of action, the toxin is considered a Tier 1 agent by the CDC, which is reserved for the most dangerous public threats. These same properties render BoNT a highly effective cosmetic and therapeutic drug (e.g., BOTOX) with diverse clinical indications. Despite decades of effort, there are no antidotes for the life-threatening consequences of botulism. This failure is primarily because the toxin hides within the nerve terminal, where it poses a challenging target for delivery of therapeutic molecules.
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[Press-News.org] New strategy to fight botulinum toxin - expert available
