Lethal neurotoxin offers unexpected hope for opioid-free painkiller

12 Jun 2019

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With opioid addiction now considered an epidemic, researchers have turned to a powerful neurotoxin to create a new type of painkiller.

In the same way that a small sample of a deadly virus can lead to an effective vaccine, researchers have found that tiny doses of a lethal neurotoxin could become an effective painkiller. Opioids remain the most common form of treating chronic and surgical pain, but their addictive nature has seen scientists work to find alternatives that are both not long-lasting and not damaging.

In a study published to Nature Communications, researchers from Boston Children’s Hospital have shown how slowly released, tiny amounts of a neurotoxin – found in marine life such as pufferfish and algae – can provide a safe, highly targeted, long-lived nerve block.

Tetrodotoxin – notorious for causing fugu poisoning from improperly prepared sashimi – was shown to effectively block sodium channels that conduct pain messages. Within lab rats, an injection of the neurotoxin showed pain relief for up to three days with no apparent sign of tissue injury.

Rather than load the readily available toxin into particles, the researchers bound it chemically to a polymer ‘backbone’. Very slowly, the body will degrade the bond between tetrodotoxin and the polymer via hydrolysis to create a natural, unorthodox painkiller.

‘Enough to kill a rat several times over’

“A lesson we learned is that with our previous delivery systems, the drug can leak out too quickly, leading to systemic toxicity,” said Daniel Kohane, who led the study. “In this system, we gave an amount of tetrodotoxin intravenously that would be enough to kill a rat several times over if given in the unbound state, and the animals didn’t even seem to notice it.”

To make it even safer for human consumption, the researchers paired the tetrodotoxin-polymer combination with a compound that made the nerve tissue more permeable. This allowed them to use smaller amounts of tetrodotoxin but still achieve nerve block.

“With the enhancer, drug concentrations that are ineffective become effective, without increasing systemic toxicity,” Kohane added. “Each bit of drug you put in packs the most punch possible.”

While tests have only been conducted in rats so far, Kohane said that, in theory, pain relief in humans could last as long as a few weeks.

Colm Gorey was a senior journalist with Silicon Republic