Snail venom inspires pain reliever
Cone snail venom has been a sources of drugs used to dull the pain of cancer, diabetes, multiple sclerosis and other conditions (Source: Phil Camill/Flickr)
Snail venom in a pill could offer powerful relief for people who suffer from severe and chronic pain.
Snails may seem an unlikely source of pharmaceutical inspiration, but the chemicals they produce have potent effects on the human nervous system.
This makes them promising sources of drugs that could dull the pain of cancer, diabetes, multiple sclerosis, HIV/AIDS, car accidents and other conditions.
In the latest advance, Australian researchers have designed a venom-inspired medication that can be taken orally - a leap forward from previous forms that needed to be injected directly into the spinal cord.
In rodent studies, the drug appears to work better than existing drugs, including morphine, at lower doses and without risks of addiction.
"Since we started getting some publicity, I've received dozens of e-mails from people all over the world asking me if they can get into clinical trials," says David Craik, a chemist at the University of Queensland, adding that he's still seeking funding and government approval before trials can begin.
"I've really been overwhelmed with some of the sad stories people have emailed," he says. "There's a great need for new treatments."
The new work involves cone snails, ocean-dwelling carnivorous predators that live in tropical waters around the world. A hungry cone snail uses a long, flexible proboscis as a lure and then as a harpoon.
Like a hypodermic needle, the proboscis injects fish, worms and other snails with venom that instantly paralyses the prey. The venom's power comes from hundreds of thousands of short proteins, called peptides.
Conotoxins
Since the 1990s, scientists have studied a few hundred of those peptides, called conotoxins, with the hope of tapping into their powers. So far, the US Food and Drug Administration has approved one synthetic conotoxin, called Prialt, for the treatment of severe and chronic pain. Others are currently in clinical trials.
While these treatments appear to work well, their biggest limitation is that they need to be injected directly into the spinal cord, often through a surgically implanted pump.
That's because the body quickly breaks down swallowed conotoxins before they can reach the receptors they need to reach.
To develop a snail-inspired painkiller stable enough to be taken orally, Craik and colleagues drew inspiration from an African plant that's long been used by witchdoctors as a tea to speed up labor and childbirth.
Chemical analyses showed that the active ingredient in the plant was a peptide with the unusual shape: a circle. That shape, it turned out, made it more stable than most peptides.
Smaller dose
Based on those findings, Craik's team engineered a synthetic conotoxin. Then, they added a few extra amino acids in order to turn the peptide into a circle.
"The advance is an elegant example of taking two lessons from nature, combining them, and making something that's even better," said Michael McIntosh, a professor of biology and psychiatry at the University of Utah School of Medicine in Salt Lake City.
When swallowed by rats with injured legs, the scientists reported in the journal Angewandte Chemie , the molecule relieved pain for more than four hours at doses more than 100 times smaller than typical doses of gabapentin, the main drug used to treat nervous system pain.
Gabapentin works for just 30% to 60% of patients, Craik adds, and it has unpleasant side effects. The new drug was also 100 times more powerful than morphine.
Because the new molecule works so well in such small concentrations, it would probably cause fewer side effects.
People with pain would be less likely to need increasingly large doses of it to keep getting relief. That, and the receptors it acts on reduce the likelihood of addiction.
Scientists have only begun to explore the pharmaceutical possibilities of a tiny fraction of compounds in cone snail venom, says Craik, let alone in all of nature. There are probably many more yet to be found.
"This points out that nature has a lot to teach us," says McIntosh. "It's essential that we preserve the sources of these natural compounds to enable further similar discoveries."
