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Breakthroughs

Creepy, Crawly Cures

By Greg Rienzi
Frank Bosmans
Frank Bosmans is an associate professor of physiology and neuroscience at the Johns Hopkins School of Medicine. His research focuses on the effects of toxins on nerve cells.

Rule No. 1: Don’t provoke the Togo starburst tarantula. This species of spider—native to West Africa and named after the celestial markings on its midsection—can move lightning fast and will bite, releasing a venom that inflicts excruciating pain and muscle cramps lasting from a few hours to a couple of weeks. Not one for the novice collector. Using such a potent venom to find new ways to treat pain in humans may seem counterintuitive, like investigating how kerosene can put out a fire, but that is essentially what transpires in the lab of physiologist Frank Bosmans.

Bosmans and his fellow researchers observe how toxins from spiders, snakes, scorpions, and other venomous creatures affect human genes. Toxins, he says, can either activate or shut down the function of a nerve cell. In nature, that’s useful, in order to kill, paralyze, or inflict serious pain on prey or deter predators.

The lab is not stacked with tanks filled with creepy, crawly creatures, thank goodness; a lab at the University of Queensland in Australia that milks the venom of more than 200 species of spiders, ships Bosmans what he needs. The researchers then “fractionate” the substance to isolate the various toxins inside. “Venom is actually a complicated cocktail of proteins, peptides, and small molecules,” says Bosmans, who early on in his career was accidentally stung by a scorpion he attempted to milk. “Venom doesn’t just target one thing, as it often affects both insect and mammal physiology.”

The larger research group that included Bosmans inserted a toxin from the Togo starburst tarantula, one of 140 toxins they tried, into an irritable bowel syndrome model, a set of neurons associated with gut pain that had been placed on a cell culture dish. Collaborators at the University of California, San Francisco, used fluorescent imaging to light up what was activated after the toxin was introduced and discovered that the toxin targets a specific sodium channel, proteins on the membranes of neurons that allow those cells to send electrical signals and trigger nervous system responses. The sodium channel, they found, plays a role in the peripheral nervous system. It regulates sensory nerves involved in mechanical pain, which is a little-explored subset of pain characterized by a hypersensitivity to stimuli that wouldn’t otherwise be painful. In migraine patients, for example, the simple act of running fingers through their hair, or other light touch after an attack, could register as pain when oversensitized nerves fire spontaneously.

The discovery could lead to new drugs that treat pain associated with such conditions as migraines, shingles, and irritable bowel syndrome, along with hypersensitivity and seizure symptoms in other conditions such as epilepsy, autism, and Alzheimer’s disease. “Now drugmakers can use this information to develop a drug that targets this sodium channel and turns off mechanical pain,” Bosmans says. Currently, there are no drugs on the market for these types of mechanical pain, as opioids, ibuprofen, and other general painkillers are ineffective.

Bosmans has already used the discovery to develop and patent a compound that can turn off the mechanical-pain gene, and preliminary evidence has shown it can inhibit gut pain, mechanical pain, and seizures in various mouse models, with no side effects.

While the toxin from the Togo starburst tarantula venom won’t be used as a drug in itself, Bosmans says some toxins can serve that purpose. He gives the example of a toxin from a cone snail that targets nerves to relieve general pain, more powerful even than morphine if injected into the spinal cord.

“The spider we used certainly doesn’t want to alleviate pain in a human. That is not the goal of this creature’s evolution. But essentially, it might help us do just that,” he says. “In studying venom from such creatures, we learned more and more about the genes that these toxins target. It’s a highly useful tool.”

spider
Portrait by Caroline Andrieu; Illustration by Alan Baker
Using venom from arachnids such as the Togo starburst tarantula, Frank Bosmans' lab studies how poison affects nerve cells in humans, with the aim of helping others develop drugs to alleviate pain.

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