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Pufferfish’s Deadly Toxin Could Help Chemo Patients

Researchers in New Jersey are working on an experimental drug that they hope will provide pain relief to cancer patients going through chemotherapy. The drug uses tetrodotoxin, the neurotoxin found in pufferfish.

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Puffer fish Image Credit: Jon Connell via Flickr

Cancer is awful. And treatments for cancer, including chemotherapy, can be incredibly painful. Even the treatments for the pain, usually opioids like morphine, can be debilitating, with side effects like dizziness, vomiting, constipation and addiction.

Because of this, medical researchers are very interested in developing alternatives to opioid medications. Researchers at the John Theurer Cancer Center at Hackensack University Medical Center, in New Jersey, are working on an experimental drug that they hope will provide pain relief to cancer patients going through chemotherapy. The drug uses tetrodotoxin, the neurotoxin found in pufferfish.

In a statement, lead investigator Dr. Samuel Goldlust said, “Tetrodotoxin has been found to be 3,000 times more potent than morphine without the negative side effects of opioids.”

Tetrodotoxin is better known for providing a dangerous allure to foodies who enjoy living on the edge. Even though pufferfish contain enough of the toxin to kill 30 people, they are considered a delicacy—delicious if prepared correctly, deadly if not.

From io9:

chefs have to be trained for two years, during which they will eat many of the fish that they themselves prepare. And make no mistake, people do die from fugu poisoning. About five people a year make puffer fish their last meal, and many more get violently sick from it. It’s not a pleasant way to go.

The poison, tetrodotoxin, is actually produced by the bacteria that the fish allows to colonize its various parts. Tetrodotoxin is a neurotoxin, meaning it takes out the nervous system as it moves through the body. This may sound like a relatively painless death, with the brain going offline quickly. That’s not the case. The toxin starts with the extremities. The first place people notice it is in the lips. Then the fingers. There’s a tingling numbness, and a loss of control. This is a sign that it’s time to get to the hospital. The toxin moves inwards from there, taking out the muscles, often causing weakness, while paradoxically bringing on vomiting and diarrhea. Then tetrodotoxin hits the diaphragm. This is the large, muscular membrane in the chest that lets the lungs breathe in and out. The respiratory system is paralyzed while the person is still fully conscious. Eventually the toxin does get to the brain, but only after the person involved has felt their body being paralyzed completely, entombing them inside. Even then, some people aren’t lucky enough to completely lose consciousness. There are people who report being conscious, either occasionally or continually, throughout their coma.

The same qualities that make tetrodotoxin so deadly—taking out parts of the nervous system—are being harnessed by these researchers to block pain signals from parts of the damaged nervous system from getting to the brain. Forty percent of patients undergoing chemotherapy report having this kind of pain, and it is one of the more common reasons that patients will cite as a reason they choose to stop chemotherapy.

Dining on pufferfish, though, isn’t even remotely a good idea for chemo patients: The treatment developed by Goldlust and WEX Pharmaceuticals uses 300 times less toxin than is found in a single puffer fish and has a very long way to go before it is available to patients. It’s currently in a phase II trial (one of about 100-300 people, according to the FDA, which looks at how effective—and, extra key in this case, how safe—the drug is) and is being tested specifically on its ability to treat patients with “chemotherapy-induced neuropathic pain”—pain caused when chemotherapy treatment damages parts of the nervous system.

There’s two more phases after this, one before and one after the drug goes to market. Only about a third of experimental drugs make it through phases I and II of testing, and phase III is the most expensive and lengthiest part of the FDA approval process. But when dealing with painkillers, particularly painkillers that are based on deadly neurotoxins, it certainly makes sense to take the time to make sure the treatment is safe.

More from Smithsonian.com:

New & Improved Fugu: Now, Without Poison!
Take That, Cancer!
The War on Cancer Goes Stealth

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