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For millions of chronic pain sufferers, big relief could come from a small sea snail. This ScienCentral News video has more.
Attacking Aches and Pains
It strikes without warning, harpooning its prey and injecting a toxic cocktail that paralyzes its victim. Despite its small size—only a few inches in length—predatory cone snails wield a venom weapon deadly enough to kill a human. Together, the chemicals in a cone snail's venom do serious damage, but each one on its own can actually do some good.
Cone snail venom is just one example of toxic tinctures researchers are turning into therapeutic treatments for chronic pain. One such drug, called Prialt, is poised for approval by the US Food and Drug Administration this fall.
Many chronic patients have tried a host of treatments, ranging from physical therapy to electrostimulation to heavy-duty drugs like morphine. "Morphine is the gold stallion for any analgesics," says Dubois. "It is very effective on pain and any new drug will likely be tested against morphine." The problem with morphine—in addition to side effects like constipation and nausea, for example—is its addictive nature. People build up a tolerance to the drug and need more and more of it to kill any pain. Venom-based medications can have their own side effects like dizziness, but patients don't build up a tolerance to the drug.
"Prialt is as effective the first day as the thirtieth day," says Toto Olivera, who pioneered research on cone snail venom some 20 years ago. A 19-year-old undergraduate first isolated the chemical, called ziconotide, on which this drug is based, back in the early 1980s. "We were just trying to figure out why cone snails were able to use their venom to paralyze their prey and why certain snail killed people. So it was really a basic science investigation and we never dreamt when we started that it would lead to a therapeutic application."
No Pain on the Brain
Brain Braun holds a picture of himself in a wheelchair he no longer needs.
"We feel pain because pain fibers carry an electrical signal to the spinal cord, and then that signal is transmitted across a gap, a synapse, to a nerve cell that then sends a signal to the brain," explains Olivera. "In order to communicate across that gap, the key thing is the electrical signal has to be converted into a chemical signal. What is important is that calcium enters the end of the pain fiber to allow the chemical signal to be released."
Administered in the right dose, ziconotide blocks the calcium gateways, so the chemical pain signal never crosses the synapse. "It blocks the transmission of the chemical across the gap, the synapse," continues Olivera. "As a result, you don't perceive any pain because your brain isn't receiving the signal."
Prialt was tested in human clinical trials over the past few years. One volunteer, Brian Braun, started using the drug in 1999, after suffering 10 years of excruciating pain that left him in a wheelchair. "I couldn't walk," says Braun. "The pain just got overwhelming." Braun's chronic pain resulted as a delayed complication to back surgery he had in 1974. "The pain began about 1989," he says. "They treated me with heavy steroids, all types of drugs, and that didn't do any good. Then I had an implanted stimulator for three years, then they started me on morphine for a good many years, but morphine just wasn't doing it." On Prialt, Braun slowly regained mobility, and no longer needs his wheelchair. He says he cooks and cleans and even cuts the grass.
Not everyone has enjoyed Braun's success with ziconotide, but his doctor, Michel Dubois, is happy to see such a good response. "If this drug has changed his life," says Dubois, "this is a major step forward in the modalities available to our patients. This drug is not for everyone, but it is definitely useful for a few selected patients who are desperately in need of help."
Meanwhile, Toto Olivera will continue to sift through the more than 50,000 individual chemicals found in the venom of the 500 different species of cone snails. His recent review of cone snail venoms was published in the January 2004 issue of Physiological Reviews, and the study was funded by the National Institute of General Medical Sciences and the Biofuture Prize for the German Ministry of Education and Research.
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