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British Columbia: New Drug From Pufferfish Could Ease Cancer Pain |
| May 11, 2004 |
Source: Vancouver Aquarium Marine Science Centre
 | A black-spotted pufferfish, Arothron nigropunctatus.
Photo: Ken Wong |
To some, pufferfish represent a collection of cartoon-like ocean oddities capable of swelling like a balloon in self-defense. To others, they are renowned as a potentially deadly delicacy whose organs secrete a fast-acting toxin if ingested. New research, however, is showing that pufferfish may also unwittingly harbour the building blocks of a scientific breakthrough – one that could give cancer patients new hope for relief from the pain associated with cancer.
A small Vancouver bioscience company has emerged as a leader in pufferfish toxin research, also known as blowfish or fugu, in the interest of developing a new pain relief medication. International Wex Technologies Inc. has just announced the beginning of phase IIb/III trails for Tectin, a powerful analgesic (pain-relieving drug) derived from the puffers’ deadly poison. The trials will involve up to 150 cancer patients and will take place in up to 25 treatment centres across Canada.
“We believe the work with blowfish toxins will contribute to the benefit of improving the quality of life to patients whose pain is not adequately controlled by currently available technologies,” said Donna Shum, Chief Operating Officer of International Wex.
Killer Bacteria
Tectin is the brand name for a highly purified form of tetrodotoxin (TTX), a toxin produced by pufferfish that causes respiratory paralysis when ingested. With no known antidote, TTX is 10,000 times more deadly than cyanide and capable of killing an adult in doses as small as one milligram. TTX is also found in several other marine animals, including the Australian blue-ringed octopus and certain types of frogs, newts and salamanders.
TTX works as a sodium channel blocker, a molecule that intercepts the electrical impulses carried from nerve cell to nerve cell by temporarily binding to sodium channel receptors on the cell membrane. The result is that the action of the nerve is halted and signals are no longer transmitted. For the purposes of pain relief, minute quantities of TTX effectively deaden pain at its source. In toxic amounts, TTX can trigger nausea, vomiting, abdominal pain, paralysis and seizures.
TTX is produced by microscopic bacteria in the skin, liver and gonads of pufferfish. The fish themselves are immune to the toxins they harbour, having evolved with a mutated sodium channel receptor in their nerve cells that TTX cannot act on. This arrangement allows for a symbiotic relationship to exist between puffer and bacteria: in return for manufacturing their deadly toxin to keep their host safe from predators, the bacteria are afforded a home inside the puffer.
“We believe the work with blowfish toxins will contribute to the benefit of improving the quality of life to patients whose pain is not adequately controlled by currently available technologies.”
-Donna Shum, COO, International Wex Technologies Inc.. |
Traditional Uses
Although this is the first time TTX has been used as a treatment for refractory cancer pain, it has long held a place in traditional medicine. In Asia, it is used to treat menstrual cramps and migraine headaches, and more recently it has been administered to heroin addicts for treatment of withdrawal symptoms. Researchers at Wex International initially began developing Tectin for the purpose of treating addiction, but found that in addition to relieving withdrawal symptoms, it was equally effective at reducing pain. It was this observation that led Wex to pursue testing of Tectin for pain relief in cancer patients.
In addition to being more powerful than morphine, two characteristics of Tectin make it a promising candidate for use in pain relief. Tectin is non-addictive, unlike morphine, and it can be administered by injection, which avoids having to administer an oral dose to patients suffering from nausea, a side effect of cancer treatment.
For the current trials, Wex Technologies is using TTX from only 2 of the 150 species of pufferfish. Proprietary technology is used to extract the compound from the waste products of puffers killed for consumption, such as yellowfin puffers (Fugu xanthopterus). The extracted quantity of TTX is so small that one puffer can yield as many as 660 doses.
The Next Phase
Phase IIa results, announced last week in Vancouver, demonstrated that Tectin can relieve refractory cancer pain – stubborn cancer pain that resists treatment – for up to two weeks in some patients.
“We are definitely encouraged by the Phase IIa results,” said Dr. Neil Hagen, Lead Investigator of the study. “We believe that the current Phase IIb/III study will be one of the largest and most important Canadian clinical trials conducted to date to evaluate the efficacy and safety of a drug for medically refractory cancer pain.”
The pivotal Phase IIb/III trial of Tectin is a randomized, placebo-controlled study, meaning that some patients will receive a Tectin injection and some will receive a placebo. The trials involve patients whose moderate-to-severe cancer pain is inadequately controlled by existing medication. The trial is expected to continue for the next 12 months, with interim results expected in 2005.
In the meantime, Tectin will also be investigated for clinical use with patients suffering from non-cancer chronic pain.
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