Toxin from a Dangerous Fish Delicacy

In tiny doses, the pufferfish’s tetrodotoxin can be turned into a pain-relieving ion channel blocker.

By Kerry Grens | January 1, 2018

© SHAYNE HILL EXTREME VISUALS/GETTY IMAGES

 

Because it’s restricted to the peripheral compartment, we think that’s why it’s so safe. It’s blocking pain from ever getting to the brain.—Christopher Gallen, Wex Pharmaceuticals

It takes only a milligram of tetrodotoxin (TTX) from improperly prepared fugu—typically made from one of a number of genera of pufferfish in Japanese or Korean cuisine—to kill an unlucky diner. Just 20 minutes after it passes a person’s lips, the tongue goes numb. Then, headache, vomiting, paralysis, and difficulty breathing can follow, and victims might die within a few hours. While tragic in the culinary setting, TTX has been a windfall for neuroscience and, if all goes well with ongoing clinical trials, may one day serve as a potent painkiller.

Since the 1960s, TTX has been a favored tool among neurophysiologists to understand cellular structure and function. It blocks sodium channels on the surface of neurons, effectively stopping their electrical transmission. Among these channels is NaV1.7, whose inhibition is known to help stop pain.

Vancouver-based Wex Pharmaceuticals is pursuing advanced clinical trials using TTX, which it harvests from the ovaries of the oblong blowfish (Takifugu oblongus), to treat cancer- and chemotherapy-related pain. In a recent Phase 3 trial with 149 participants, those receiving 30 μg of TTX twice a day for four days were more likely to report reduced pain than were those who received a placebo (Pain Res Manag, 2017:7212713, 2017).

The study didn’t hit all the statistical marks, but Wex’s CEO Christopher Gallen says there is enough promise in the results to pursue another Phase 3 study. Most appealing is the apparent lack of serious side effects, something Gallen attributes to “sheer luck”: the charge and shape of the molecule keep it from crossing the blood-brain barrier. “The molecule does not look like anything a chemist would want to design,” he says. “Because it’s restricted to the peripheral compartment, we think that’s why it’s so safe . . . It’s blocking pain from ever getting to the brain.”

Read about other animal groups researchers are exploring for pain-killing leads in the full feature story, “Animal Analgesics.”

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