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Pufferfish pain relief? Doctors use fish’s neurotoxin to improve lives of cancer patients

Pufferfish puffer fish 2 istock.jpg

The pufferfish is most well-known for its unique bloated shape and prickly self-defense mechanism.  It also has a reputation for being lethal: the creature secretes a deadly neurotoxin in some of its internal organs and on its skin, often making the fish a fatal meal for predators.

But the pufferfish’s fame may one day extend beyond its interesting appearance and poisonous qualities. The fish may soon be known for helping to improve the lives of cancer patients.

Researchers at the Brain and Spine Institute at the John Theurer Cancer Center at Hackensack University Medical Center in New Jersey are leading a phase II clinical trial, hoping to harness the effects of Tetrodotoxin, a neurotoxin found in pufferfish.  The research team, led by principle investigator Dr. Samuel Goldlust, hopes to utilize Tetrodotoxin (TTX) in new medications aimed at treating chemotherapy-induced neuropathic pain, an often debilitating condition experienced by more than 40 percent of patients undergoing chemotherapy treatments.

“We have a fairly busy cancer center with one of the highest patient volumes in the country,” Goldlust, co-chief of the Brain and Spine Institute, told FoxNews.com.  “A substantial portion of those patients are on chemo drugs that cause neuropathy, which covers the gamut from damage of nerves in hands to the feet...Patients can experience anything from numbness (in the extremities) to extremely severe pain and can even be wheelchair-bound.”

Current medications used to treat neuropathy are often opioid-based painkillers, including drugs like Percocet and morphine.  While effective, these types of medicines typically come with a host of side effects, such as confusion, major gastrointestinal tract issues, hallucinations and more.

Anti-convulsion medication and anti-depressants have also been used to treat chemotherapy-induced pain, but they, too, have been shown to cause significant side effects and can even interfere with the chemo’s effectiveness.

Goldlust said that TTX is an attractive alternative to these medications, since the right amount of the substance can ease neuropathy symptoms without creating any unwanted side effects.  TTX works by blocking the main electrical pathway responsible for transmitting pain signals.

“The normal systems that nerves use to transmit pain signals from the hand or the foot up to the brain – they use a system of sodium channels, which are just like sodium in our diet,” Goldlust said. “If those channels are blocked, then you can block those pain signals.”

For predators that mistakenly munch on a pufferfish, the TTX located in the fish’s body prevents the predator’s nerves from sending signals to one another, leading them to ultimately cease functioning.  And for humans, the neurotoxin is just as deadly if consumed, considered to be 100 times more lethal than cyanide.  Therefore, finding the right dosage of TTX for patients is crucial, Goldlust said.  Just enough can dull or quiet the chemo-induced pain – but too much could cause the extremities to become numb.

Goldlust and his team received a drug made with TTX in a phase II clinical trial from WEX Pharmaceuticals.  It was first tested in health volunteers and participants involved in general pain studies.  The drug came to the Brain and Spine Institute at John Theurer after the company felt there was an unmet need for cancer patients.

In the trial, the researchers administered the TTX-based drug via subcutaneous injection, twice a day for five days.  The patients involved in the study had all completed chemotherapy treatments and were suffering residual pain from the chemo they had received.  According to Goldlust, patients who received just five days of the treatment experienced up to two months of pain relief.

“If (these patients) are suffering from pain day to day, you have gone from one battle but now you’re suffering from another,” Goldlust said.  “We find that patients don’t want to seem unappreciative, but a lot of people are suffering from this.  As the trial started, we’ve seen more and more people that have volunteered for the study.  At first they didn’t want to seem ungrateful, but they were truly suffering – and it’s brought a lot of these people out.”

Currently, the research team is focusing on finding the right dosage for the TTX-based drug, before moving on to phase III clinical trial, during which the medication would be administered to an even larger group of people.  If the next phase proves successful, they hope to send the medication to the Food and Drug Administration (FDA) for approval.

But once their research is over, there is still more work to be done on TTX.

“Once we’ve completed this study, there’s a wide array of patients we can use it for, such as those with diabetic related neuropathy – which affects millions per year,” Goldlust said.  “Diabetes is a wide spread issue in this country, and there’s a lot of people with undertreated pain, so we’re hoping to apply it to things like that.”